65 results on '"Ahmad J. Obaidullah"'
Search Results
2. Discovery of Novel Coumarin-Schiff Base Hybrids as Potential Acetylcholinesterase Inhibitors: Design, Synthesis, Enzyme Inhibition, and Computational Studies
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Jamalis, Aso Hameed Hasan, Faruq Azeez Abdulrahman, Ahmad J. Obaidullah, Hadil Faris Alotaibi, Mohammed M. Alanazi, Mahmoud A. Noamaan, Sankaranarayanan Murugesan, Syazwani Itri Amran, Ajmal R. Bhat, and Joazaizulfazli
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acetylcholinesterase ,Schiff base ,coumarin ,DFT ,chemical reactivity ,molecular modeling ,drug likeness - Abstract
To discover anti-acetylcholinesterase agents for the treatment of Alzheimer’s disease (AD), a series of novel Schiff base-coumarin hybrids was rationally designed, synthesized successfully, and structurally characterized using Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR), and High-Resolution Mass Spectrometry (HRMS) analyses. These hybrids were evaluated for their potential inhibitory effect on acetylcholinesterase (AChE). All of them exhibited excellent inhibitory activity against AChE. The IC50 values ranged from 87.84 to 515.59 μg/mL; hybrids 13c and 13d with IC50 values of 0.232 ± 0.011 and 0.190 ± 0.004 µM, respectively, showed the most potent activity as acetylcholinesterase inhibitors (AChEIs). The reference drug, Galantamine, yielded an IC50 of 1.142 ± 0.027 µM. Reactivity descriptors, including chemical potential (μ), chemical hardness (η), electrophilicity (ω), condensed Fukui function, and dual descriptors are calculated at wB97XD/6-311++ G (d,p) to identify reactivity changes of the designed compounds. An in-depth investigation of the natural charge pattern of the studied compounds led to a deep understanding of the important interaction centers between these compounds and the biological receptors of AChE. The molecular electrostatic surface potential (MESP) of the most active site in these derivatives was determined using high-quality information and visualization. Molecular docking analysis was performed to predict binding sites and binding energies. The structure-activity-property relationship studies indicated that the proposed compounds exhibit good oral bioavailability properties. To explore the stability and dynamic behavior of the ligand-receptor complexes, molecular dynamics simulations (MDS) were performed for 100 ns on the two best docked derivatives, 13c and 13d, with the AChE (4EY7) receptor. A popular method for determining the free binding energies (MM/GBSA) is performed using snapshots taken from the systems’ trajectories at 100 ns. These results revealed that the complex system of compound 13d acquired a relatively more stable conformation and exhibited better descriptors than the complex system of compound 13c and the Galantamine drug, suggesting its potential as an effective inhibiting drug. The binding free energy analysis revealed that the 13d-4EY7 complex exhibited greater stability with AChE receptors compared to other complexes.
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- 2023
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3. Controlled Size Oils Based Green Fabrication of Silver Nanoparticles for Photocatalytic and Antimicrobial Application
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Alanazi, Seemab Pervaiz, Iram Bibi, Wajid Rehman, Hadil Faris Alotaibi, Ahmad J. Obaidullah, Liaqat Rasheed, and Mohammed M.
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silver nanoparticles (Ag-NPs) ,clove oil ,cinnamon oil ,cardamom oil ,agglomeration ,size homogeneity and crystallite size - Abstract
The particle size at the nanometric level allows the manifestation of remarkable properties, chiefly due to changes in surface-to-volume ratio. This study is attributed to the novel green synthesis of nano silver by using essential oils as a capping and reducing agent. Clove oil, cinnamon oil, and cardamom oil were selected for the eco-friendly and low-cost fabrication of silver nanoparticles. The prepared nanoparticles were characterized by photoluminescence spectroscopy, FT-IR spectroscopy, X-Ray diffraction, energy dispersive X-ray spectroscopy, dynamic laser light scattering, thermogravimetric analysis, and transmission electron microscopy. It was found that samples prepared by using cinnamon oil (20 nm) and cardamom oil (12 nm) had smaller particle sizes as compared to those synthesized by using clove oil (45 nm). All the prepared samples exhibited very strong antimicrobial activities with a clear zone of inhibition (6–24 mm) against Staphylococcus aureus, Klebsiella pneumoniae, and Candida albicans. Very resilient photocatalytic activities of the samples were observed against Allura red and fast green dyes. It was concluded that the cinnamon oil-based system is the best size reducer and size homogenizer (less chances of agglomeration) as compared to clove oil and cardamom oil (more chances of agglomeration) for the synthesis of silver nanoparticles.
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- 2023
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4. In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives
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Khafagy, Amr Selim Abu Lila, Mohammed Amran, Mohamed A. Tantawy, Ehssan H. Moglad, Shadeed Gad, Hadil Faris Alotaibi, Ahmad J. Obaidullah, and El-Sayed
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antitumor activity ,Ehrlich ascites carcinoma ,MTT assay ,nanocapsule ,pyridine derivatives - Abstract
This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.
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- 2023
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5. Facile Synthesis and Characterization of Fe0.5Mn0.5Co2O4/Fe2O3 as a Novel Nanocomposite for the Effective Photocatalytic Decomposition of Safranin Dye
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Asma S. Al-Wasidi, Abdulrahman A. Almehizia, Hamad M. Alkahtani, Ahmad J. Obaidullah, Ahmed M. Naglah, Eida S. Al-Farraj, M. Khairy, Gharieb S. El-Sayyad, and Ehab A. Abdelrahman
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Polymers and Plastics ,Materials Chemistry - Published
- 2023
6. Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2
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Heba I. Ghamry, Amany Belal, Mohamed Kandeel El-Ashrey, Haytham O. Tawfik, Reem I. Alsantali, Ahmad J. Obaidullah, Ahmed A. El-Mansi, and Doaa Abdelrahman
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Multidisciplinary - Abstract
Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus's multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1). Pharmacophore mapping, molecular docking, and dynamic studies were conducted over 50 ns and 100 ns on a panel of 39 natural phenolic acids. Rosmarinic acid (16) on the Mpro receptor (− 16.33 kcal/mol) and tannic acid (17) on the AAK1 receptor (− 17.15 kcal/mol) exhibited the best docking energy against both receptors. These favourable docking score values were found to be superior to those of the co-crystallized ligands. Preclinical and clinical research is required before using them simultaneously to halt the COVID-19 life cycle in a synergistic manner.
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- 2023
7. Synthesis, Spectroscopic Characterization and Thermal Studies of Polymer-Metal Complexes Derived from Modified Poly Styrene-Alt-(Maleic Anhydride) as a Prospects for Biomedical Applications
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Abdulrahman A. Almehizia, Hamad M. Alkahtani, Mohamed A. Al-Omar, Ahmad J. Obaidullah, Mashooq A. Bhat, Lamees S. Alrasheed, Ahmed M. Naglah, Ayman A. O. Younes, Amnah Mohammed Alsuhaibani, Moamen S. Refat, Abdel Majid A. Adam, Mohamed Y. El-Sayed, and Kareem A. Asla
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Inorganic Chemistry ,General Chemical Engineering ,complexes ,transition metal ions ,thermal analysis ,spectral analysis ,poly styrene-alt-(maleic anhydride) ,General Materials Science ,Condensed Matter Physics - Abstract
Eight polymer-metal complexes were synthesized from complexation of divalent Mn(II), Ni(II), Co(II), and Cu(II) metal ions with modified polystyrene-alt-(maleic anhydride) (PSMAP and PSMAM) ligands. The structures of these new complexes were characterized using a variety of techniques, including magnetic moment susceptibility, conductance measurements, FT-IR spectroscopy, ultraviolet-visible (UV-VIS), thermogravimetric analysis (TGA), as well as scanning electron microscopy (SEM). All metal-polymer complexes have a non-electrolytic nature based on conductance measurements. The polymer molecule behaves as neutral bidentate NO ligand through O atoms of carbonyl (C=O) and N atoms of amide (O=C-NH). Divalent Mn2+, Ni2+, Co2+ and Cu2+ complexes have an octahedral geometry based on their electronic spectra and magnetic values. Based on thermal analysis data, those new complexes are more thermally stable than the ligands. SEM and TEM are manipulated to give the surface structure and the particle size measurements where they give different shapes and sizes of the synthesized complexes.
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- 2023
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8. Antibacterial Efficacy of N-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-β-Lactamase Producing Clinical Strain of Escherichia coli ST 131
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Gulraiz Ahmad, Aqsa Khalid, Muhammad Usman Qamar, Nasir Rasool, Malik Saadullah, Muhammad Bilal, Majed A. Bajaber, Ahmad J. Obaidullah, Hadil Faris Alotaibi, and Jawaher M. Alotaibi
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ESBL-producing E. coli ,ST131 ,blaCTX-M ,carboxamides ,docking analysis ,Chemistry (miscellaneous) ,Organic Chemistry ,Drug Discovery ,Molecular Medicine ,Pharmaceutical Science ,Physical and Theoretical Chemistry ,Analytical Chemistry - Abstract
Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum β-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a–h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate’s identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a–h) demonstrated the binding pocket residues involved in the active site of the β-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the β-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds.
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- 2023
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9. Bis-indole based triazine derivatives: Synthesis, characterization, in vitro β-glucuronidase anti-cancer and anti-bacterial evaluation along with in silico molecular docking and ADME analysis
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Shoaib Khan, Wajid Rehman, Fazal Rahim, Rafaqat Hussain, Ahmad J. Obaidullah, Hadil Faris Alotaibi, Mohammed M. Alanazi, Muhammad Usman Khan, and Yousaf Khan
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General Chemical Engineering ,General Chemistry - Published
- 2023
10. Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach
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Engy Elekhnawy, Walaa A. Negm, Mona El-Aasr, Amal Abo Kamer, Mohammed Alqarni, Gaber El-Saber Batiha, Ahmad J. Obaidullah, and Heba M. Fawzy
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Indoles ,Science ,Microbial Sensitivity Tests ,Article ,Applied microbiology ,Bacterial Proteins ,Animals ,Pseudomonas Infections ,Multidisciplinary ,Bacteria ,Plant Extracts ,Antimicrobials ,Chromobacterium ,Quorum Sensing ,Gene Expression Regulation, Bacterial ,Skin Diseases, Bacterial ,biochemical phenomena, metabolism, and nutrition ,Anti-Bacterial Agents ,Rats ,Disease Models, Animal ,Biofilms ,Zamiaceae ,Pseudomonas aeruginosa ,Medicine ,Female - Abstract
Pseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.
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- 2022
11. Renewed global threat by the novel SARS-CoV-2 variants ‘XBB, BF.7, BQ.1, BA.2.75, BA.4.6’: A discussion
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Ranjan K. Mohapatra, Ahmed Mahal, LV Simhachalam Kutikuppala, Madhumita Pal, Venkataramana Kandi, Ashish K. Sarangi, Ahmad J. Obaidullah, and Snehasish Mishra
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General Medicine - Published
- 2022
12. A Novel Green Micellar HPLC-UV Method for the Estimation of Vandetanib in Pure Form, Human Urine, Human Plasma and Human Liver Microsomes Matrices with Application to Metabolic Stability Evaluation
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AHMAD J OBAIDULLAH, Mohamed Attwa, and Mohammed Alanazi
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Chemistry (miscellaneous) ,Organic Chemistry ,Drug Discovery ,Molecular Medicine ,Pharmaceutical Science ,Physical and Theoretical Chemistry ,green chemistry ,vandetanib ,human urine ,human plasma ,human liver microsomes ,Analytical Chemistry - Abstract
Vandetanib (Caprelsa®; VNB) is a prescription medicine that is used for the treatment of medullary thyroid cancer that has disrupted other body parts or that cannot be removed by surgery. It is considered a tyrosine kinase inhibitor (TKI). Fast, sensitive and validated HPLC–UV was established for VNB quantification in pure human biological fluids (urine and plasma) and human liver microsomes (HLMs). This analytical methodology was applied also to the metabolic stability assessment of VNB. This method was performed using a phenyl column (250 mm × 4.6 mm id, 5 µm particle size). A sodium dodecyl sulphate solution (0.05 M, pH 3.0 using 0.02 M orthophosphoric acid) containing 0.3% triethylamine and 10% n-butanol was used as a mobile phase and was pumped isocratically at a flow rate of 0.7 mL/min and at a 260 nm detection wavelength. The total elution time was 6 min with an injection volume of 20 μL. The linearity of the established methodology ranged from 30 to 500 ng/mL in pure form and 50 to 500 ng/mL (r2 ≥ 0.9994) in human biological fluids and HLMs. No significant interference from the matrix components was observed. The proposed methodology revealed the benefits of being green, reliable and economic.
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- 2022
13. Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors
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Hamad M. Alkahtani, Amer Alhaj Zen, Ahmad J. Obaidullah, Mohammed M. Alanazi, Abdulrahman A. Almehizia, Siddique Akber Ansari, Fadilah Sfouq Aleanizy, Fulwah Yahya Alqahtani, Rana M. Aldossari, Raghad Abdullah Algamdi, Lamees S. Al-Rasheed, Sami G. Abdel-Hamided, Alaa A.-M. Abdel-Aziz, and Adel S. El-Azab
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Chemistry (miscellaneous) ,Organic Chemistry ,Drug Discovery ,Molecular Medicine ,Pharmaceutical Science ,Physical and Theoretical Chemistry ,quinazolinones ,cytotoxic agents ,CDK9 ,molecular docking ,Analytical Chemistry - Abstract
Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski’s rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.
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- 2022
14. Design, synthesis and molecular docking of new [1,2,4] triazolo[4,3-a]quinoxaline derivatives as anticancer agents targeting VEGFR-2 kinase
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Ahmad J. Obaidullah, Hussam Albassam, Mohammed S Taghour, Nawaf A. Alsaif, Hazem A. Mahdy, Alaa Elwan, Wael A. Alanazi, Mohammed M. Alanazi, and Abdullah F. Alasmari
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Sorafenib ,Chemistry ,Kinase ,Organic Chemistry ,General Medicine ,Catalysis ,In vitro ,Inorganic Chemistry ,Vascular endothelial growth factor ,chemistry.chemical_compound ,Quinoxaline ,Biochemistry ,Docking (molecular) ,Drug Discovery ,medicine ,Physical and Theoretical Chemistry ,Cytotoxicity ,Molecular Biology ,IC50 ,Information Systems ,medicine.drug - Abstract
Vascular endothelial growth factor receptor-2 (VEGFR-2) is critically involved in cancer angiogenesis. Blocking of VEGFR-2 signaling pathway proved effective suppression of tumor growth. Accordingly, two series of new triazoloquinoxaline-based derivatives were designed and synthesized as VEGFR-2 inhibitors. All in vitro cytotoxic activities of the synthesized compounds were evaluated against two human cancer cell lines (MCF-7 and HepG2). To confirm the potential mechanism of cytotoxicity, enzymatic assays against VEGFR-2 were estimated for all the target compounds. The results of VEGFR-2 inhibitory activity and cytotoxicity were in high correlation. Compound 22a exhibited the highest cytotoxic effect with IC50 values of 6.2 and 4.9 μM against MCF-7 and HepG2, respectively, comparing to sorafenib (IC50 = 3.53 and 2.18 μM). Such derivative showed the best VEGFR-2 inhibitory activity with an IC50 value of 3.9 nM, which is very close to that of sorafenib (IC50 = 3.13 nM). Moreover, compounds 22b, 23b, and 23e exhibited strong cytotoxic activity with IC50 values ranging from 11.7 to 15.3 μM. Also, these compounds showed promising VEGFR-2 inhibition with IC50 values of 4.2, 5.7, and 4.7 nM, respectively. In silico docking, ADMET, and toxicity studies were carried out for the synthesized compounds. The results revealed that some compounds have a good binding mode against VEGFR-2 and a high level of drug-likeness.
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- 2021
15. Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers
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Ahmad J. Obaidullah, Ibrahim H. Eissa, Alaa Elwan, Nawaf A. Alsaif, Abdullah F. Alasmari, Wael A. Alanazi, Mohammed M. Alanazi, Hussam Albassam, and Hazem Elkady
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VEGF receptors ,Antineoplastic Agents ,RM1-950 ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Inducer ,Pharmacology ,integumentary system ,biology ,apoptosis ,3-methylquinoxalin ,General Medicine ,molecular docking ,Cancer angiogenesis ,Vascular Endothelial Growth Factor Receptor-2 ,Vascular endothelial growth factor ,Molecular Docking Simulation ,VEGFR-2 ,Anticancer ,chemistry ,Design synthesis ,Apoptosis ,Docking (molecular) ,Drug Design ,embryonic structures ,cardiovascular system ,Cancer research ,biology.protein ,Therapeutics. Pharmacology ,Drug Screening Assays, Antitumor ,Research Article ,Research Paper - Abstract
Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a critical role in cancer angiogenesis. Inhibition of VEGFR-2 activity proved effective suppression of tumour propagation. Accordingly, two series of new 3-methylquinoxaline derivatives have been designed and synthesised as VEGFR-2 inhibitors. The synthesised derivatives were evaluated in vitro for their cytotoxic activities against MCF-7and HepG2 cell lines. In addition, the VEGFR-2 inhibitory activities of the target compounds were estimated to indicate the potential mechanism of their cytotoxicity. To a great extent, the results of VEGFR-2 inhibition were highly correlated with that of cytotoxicity. Compound 27a was the most potent VEGFR-2 inhibitor with IC50 of 3.2 nM very close to positive control sorafenib (IC50 = 3.12 nM). Such compound exhibited a strong cytotoxic effect against MCF-7 and HepG2, respectively with IC50 of 7.7 and 4.5 µM in comparison to sorafenib (IC50 = 3.51 and 2.17 µM). In addition, compounds 28, 30f, 30i, and 31b exhibited excellent VEGFR-2 inhibition activities (IC50 range from 4.2 to 6.1 nM) with promising cytotoxic activity. Cell cycle progression and apoptosis induction were investigated for the most active member 27a. Also, the effect of 27a on the level of caspase-3, caspase-9, and BAX/Bcl-2 ratio was determined. Molecular docking studies were implemented to interpret the binding mode of the target compounds with the VEGFR-2 pocket. Furthermore, toxicity and ADMET calculations were performed for the synthesised compounds to study their pharmacokinetic profiles
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- 2021
16. Assessment of solid-dosage drug nanonization by theoretical advanced models: Modeling of solubility variations using hybrid machine learning models
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Amr S. Abouzied, Saad M. Alshahrani, Umme Hani, Ahmad J. Obaidullah, Ahmed Abdullah Al Awadh, Ahmed A. Lahiq, and Halah Jawad Al-fanhrawi
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Fluid Flow and Transfer Processes ,Engineering (miscellaneous) - Published
- 2023
17. Computational intelligence modeling of nanomedicine preparation using advanced processing: Solubility of fludrocortisone acetate in supercritical carbon dioxide
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Umme Hani, Zainab Ali Bu sinnah, Ahmad J. Obaidullah, Bader Huwaimel, Muteb Alanazi, Tareq Nafea Alharby, Ahmed A. Lahiq, and Abdullah Ali Alshehri
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Fluid Flow and Transfer Processes ,Engineering (miscellaneous) - Published
- 2023
18. Inhibition of
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Kaoutar, Benrahou, Hanae, Naceiri Mrabti, Abdelhakim, Bouyahya, Nour Elhouda, Daoudi, Mohamed, Bnouham, Hicham, Mezzour, Shafi, Mahmud, Mohammed Merae, Alshahrani, Ahmad J, Obaidullah, Yahia, Cherrah, and My El Abbes, Faouzi
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- 2022
19. Molecular Docking and Dynamics Simulation of Natural Compounds from Betel Leaves (
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Sabbir, Ahmed, Md Chayan, Ali, Rumana Akter, Ruma, Shafi, Mahmud, Gobindo Kumar, Paul, Md Abu, Saleh, Mohammed Merae, Alshahrani, Ahmad J, Obaidullah, Sudhangshu Kumar, Biswas, Md Mafizur, Rahman, Md Mizanur, Rahman, and Md Rezuanul, Islam
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Molecular Docking Simulation ,Diabetes Mellitus, Type 2 ,Glucosides ,Humans ,Glycoside Hydrolase Inhibitors ,alpha-Glucosidases ,Apigenin ,Molecular Dynamics Simulation ,alpha-Amylases ,Piper betle - Published
- 2022
20. The Emergence of SARS-CoV-2 Variants With a Lower Antibody Response: A Genomic and Clinical Perspective
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Suvro Biswas, Shafi Mahmud, Mohasana Akter Mita, Shamima Afrose, Md. Robiul Hasan, Gobindo Kumar Paul, Mst. Sharmin Sultana Shimu, Md. Salah Uddin, Shahriar Zaman, Moon Nyeo Park, Abolghasem Siyadatpanah, Ahmad J. Obaidullah, Md. Abu Saleh, Jesus Simal-Gandara, and Bonglee Kim
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General Medicine - Abstract
The emergence of several novel SARS-CoV-2 variants regarded as variants of concern (VOCs) has exacerbated pathogenic and immunologic prominences, as well as reduced diagnostic sensitivity due to phenotype modification-capable mutations. Furthermore, latent and more virulent strains that have arisen as a result of unique mutations with increased evolutionary potential represent a threat to vaccine effectiveness in terms of incoming and existing variants. As a result, resisting natural immunity, which leads to higher reinfection rates, and avoiding vaccination-induced immunization, which leads to a lack of vaccine effectiveness, has become a crucial problem for public health around the world. This study attempts to review the genomic variation and pandemic impact of emerging variations of concern based on clinical characteristics management and immunization effectiveness. The goal of this study is to gain a better understanding of the link between genome level polymorphism, clinical symptom manifestation, and current vaccination in the instance of VOCs.
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- 2022
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21. Application of Nanosized Zeolite X Modified with Glutamic Acid as a Novel Composite for the Efficient Removal of Co(II) ions from Aqueous Media
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Ahmed M. Naglah, Mashooq A. Bhat, Nasser S. Al-Shakliah, Mohamed A. Al-Omar, Ahmad J. Obaidullah, Abdulrahman A. Almehizia, and Hamad M. Alkahtani
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Exothermic reaction ,Langmuir ,Materials science ,Polymers and Plastics ,Composite number ,02 engineering and technology ,Crystal structure ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Amorphous solid ,Ion ,Adsorption ,Materials Chemistry ,0210 nano-technology ,Zeolite ,Nuclear chemistry - Abstract
In this work, nanosized zeolite X modified with glutamic acid was facilely synthesized as a novel composite. Also, the synthesized zeolite X/glutamic acid composite was identified using various instruments such as XRD, CHN, FT-IR, and FE-SEM. The FE-SEM image confirmed that the fabricated composite has a cotton-like structure. Also, the XRD pattern confirmed the presence of a wide XRD peak at 2Ɵ = 23°. Hence, this confirmed that the crystalline structure of zeolite X interfered or combined over amorphous surroundings. Besides, the synthesized zeolite X/glutamic acid composite was employed as an adsorbent for the efficient removal of Co(II) ions from aqueous media. Moreover, the highest removal efficiency is achieved at pH = 6, time = 100 min, and temperature = 298 K. The experimental results were matched well with the Langmuir equilibrium isotherm and pseudo-second-order kinetic model. The maximum adsorption capacity of the synthesized composite is 120.90 ± 3.94 mg/g. Additionally, the removal of Co(II) ions is chemical, exothermic, and spontaneous.
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- 2021
22. Synthesis of Low-Cost, Bio-Based Novel Adsorbent Material Using Charge-Transfer Interaction for Water Treatment from Several Pollutants: Waste to Worth
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Abdulrahman A. Almehizia, Mohamed A. Al-Omar, Ahmed M. Naglah, Hamad M. Alkahtani, Ahmad J. Obaidullah, and Mashooq A. Bhat
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Inorganic Chemistry ,General Chemical Engineering ,General Materials Science ,charge-transfer interaction ,vacant orbital acceptor ,metal oxide composite ,waste tea leaves ,activated carbons ,adsorption of contaminants ,Condensed Matter Physics - Abstract
Tea is the third most consumed beverage in Saudi Arabia (a country in the Middle East) after water and Arabian coffee. Hence, a large amount of consumed tea leaves is discarded as solid waste. Waste tea leaves (WTLs) have no commercial value and could be considered as an environmentally sustainable costless material. This work aimed to manufacture an adsorbent material from the discarded WTLs and charge-transfer (CT) interaction and use this adsorbent material effectively for the removal of different kinds of pollutants from water. The adsorbent material was manufactured in three steps. First, a CrFeO3 metal composite was synthesized from the CT interaction between FeCl3 and CrCl3 with urea. Second, activated carbons were prepared from consumed WTLs using facile and clean treatments of pre-carbonization, and a simple potassium hydroxide (KOH) activation treatment. Finally, the adsorbent material was fabricated by grounding CrFeO3 composite with the activated carbons in a 1:10 molar ratio (metal composite to activated carbons). The prepared materials were characterized spectroscopically and morphologically using FT-IR, XRD, SEM/EDX, and TEM analysis. The synthesized absorbent material was used to adsorb two organic dyes (Azocarmine G2; M1, and Methyl violet 2B; M2), and two commercial pesticides (Tiller 480SL; M3, and Acochem 25% WP; M4) from aqueous solution, and it showed promising adsorption efficacy. The minimum adsorbent material’s dosage to obtain a maximum removal efficiency (R%) for M1, M2, M3, and M4 removal from 100 mL solution (100 mg/L) was 0.11, 0.14, 0.13, and 0.12 g, respectively. The max R% for M1 (96.8%) was achieved in the first 45 min, the max R% for M2, 95.5%, was achieved during the first 55 min, and the max R% for M3 (96.4%) was achieved in the first 35 min, while the max R% for M4, 98.6%, was achieved during the first 35 min.
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- 2023
23. Synthesis, antiproliferative and enzymatic inhibition activities of quinazolines incorporating benzenesulfonamide: Cell cycle analysis and molecular modeling study
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Adel S. El-Azab, Hamad M. Alkahtani, Nawaf A. AlSaif, Ibrahim A. Al-Suwaidan, Ahmad J. Obaidullah, Mohammed M. Alanazi, Abdulrahman M. Al-Obaid, Mohamed H.M. Al-Agamy, and Alaa A.-M. Abdel-Aziz
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Inorganic Chemistry ,Organic Chemistry ,Spectroscopy ,Analytical Chemistry - Published
- 2023
24. Synthesis of Bivalent Ni(II), Cu(II) and Zn(II) Complexes of Azodicarbonamide in Mixture of Methanol and Aqueous Solvents: Spectral Characterizations and Anti-Microbial Studies
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Ayman A. O. Younes, Abdel Majid A. Adam, Moamen S. Refat, Asma S. Al-Wasidi, Abdulrahman A. Almehizia, Mohamed A. Al-Omar, Ahmed M. Naglah, Abdulrahman M. Al-Obaid, Hamad M. Alkahtani, Ahmad J. Obaidullah, Mohamed Y. El-Sayed, and Kareem A. Asla
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Inorganic Chemistry ,azodicarbonamide ,transition metal complexes ,bioactivity ,thermal analysis ,optical properties ,General Chemical Engineering ,General Materials Science ,Condensed Matter Physics - Abstract
Three new transition-metal complexes were produced by refluxing azodicarbonamide (ADCA) with nickel(II), copper(II), and zinc(II) solutions in a mixture of 50% (v/v) methanol and water. The magnitude of chelation between metal ions and ligand molecules was assessed by FT-IR, UV, elemental analysis, TGA, conductivity, mass, and magnetic susceptibility measurements. FT-IR analysis suggested a bi-dentate chelation in all complexes, which takes place through the N-azo and O-carbonyl groups. Based on the measurement of magnetic moments and spectral analysis, a distorted octahedral geometry was proposed for Ni(II) and Cu(II) complexes, whereas zinc complex showed a hexa-coordinated geometry. The optical band gaps of the nickel(II), copper(II) and zinc(II) complexes were found to be 1.91, 2.50, and 1.96 eV, respectively, which means that they can be employed as semiconductors and that they are in the same range as highly effective photovoltaic materials. The Urbach energy parameters were also estimated from other optical parameters. The biological activity of azodicarbonamide and its synthesized complexes has been screened against the selected gram bacteria (+ve) and fungi.
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- 2023
25. New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with in silico docking, ADMET, toxicity, and DFT studies
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Mohammed M. Alanazi, Ahmad J. Obaidullah, Nawaf A. Alsaif, Madhawi A. Alharbi, Manal M. Alanazi, Ibrahim H. Eissa, Hamad M. Alkahtani, Mohammed A. Dahab, and Hazem Elkady
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chemistry.chemical_classification ,Cell cycle checkpoint ,biology ,General Chemical Engineering ,In silico ,Active site ,General Chemistry ,Cell cycle ,chemistry.chemical_compound ,Quinoxaline ,Enzyme ,chemistry ,Biochemistry ,Apoptosis ,Docking (molecular) ,biology.protein - Abstract
A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC50 ranging from 2.3 to 5.8 μM. An enzymatic assay was carried out for all the tested candidates against VEGFR-2. Compound 17b was the most potent VEGFR-2 inhibitor (IC50 = 2.7 nM). Mechanistic investigation including cell cycle arrest and apoptosis was performed for compound 17b against HepG-2 cells, and the results revealed that 17b induced cell apoptosis and arrested cell cycle in the G2/M phase. Moreover, apoptosis analyses were conducted for compound 17b to evaluate its apoptotic potential. The results showed upregulation in caspase-3 and caspase-9 levels, and improving the Bax/Bcl-2 ratio by more than 10-fold. Docking studies were performed to determine the possible interaction with the VEGFR-2 active site. Further docking studies were carried out for compound 17b against cytochrome P450 to present such compounds as non-inhibitors. In silico ADMET, toxicity, and physico-chemical properties revealed that most of the synthesized members have acceptable values of drug-likeness. Finally, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties.
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- 2021
26. Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and in silico studies
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Ahmad J. Obaidullah, Sultan M. Alsubaie, Mohammed M. Alanazi, Mohammed S Taghour, Nawaf A. Alsaif, Elwan Alaa, Hamad M. Alkahtani, Ibrahim H. Eissa, and Abdulrahman A. Almehizia
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Pharmacology ,Sorafenib ,Chemistry ,In silico ,apoptosis ,3-methylquinoxalin-2(1h)-one ,General Medicine ,RM1-950 ,Cell cycle ,anticancer ,In vitro ,3-methylquinoxaline-2-thiol ,in silico studies ,Apoptosis ,Docking (molecular) ,Drug Discovery ,medicine ,Therapeutics. Pharmacology ,Cytotoxicity ,IC50 ,vegfr-2 inhibitors ,medicine.drug - Abstract
There is an urgent need to design new anticancer agents that can prevent cancer cell proliferation even with minimal side effects. Accordingly, two new series of 3-methylquinoxalin-2(1H)-one and 3-methylquinoxaline-2-thiol derivatives were designed to act as VEGFR-2 inhibitors. The designed derivatives were synthesised and evaluated in vitro as cytotoxic agents against two human cancer cell lines namely, HepG-2 and MCF-7. Also, the synthesised derivatives were assessed for their VEGFR-2inhibitory effect. The most promising member 11e were further investigated to reach a valuable insight about its apoptotic effect through cell cycle and apoptosis analyses. Moreover, deep investigations were carried out for compound 11e using western-plot analyses to detect its effect against some apoptotic and apoptotic parameters including caspase-9, caspase-3, BAX, and Bcl-2. Many in silico investigations including docking, ADMET, toxicity studies were performed to predict binding affinity, pharmacokinetic, drug likeness, and toxicity of the synthesised compounds. The results revealed that compounds 11e, 11g, 12e, 12g, and 12k exhibited promising cytotoxic activities (IC50 range is 2.1 - 9.8 µM), comparing to sorafenib (IC50 = 3.4 and 2.2 µM against MCF-7 and HepG2, respectively). Moreover, 11b, 11f, 11g, 12e, 12f, 12g, and 12k showed the highest VEGFR-2 inhibitory activities (IC50 range is 2.9 - 5.4 µM), comparing to sorafenib (IC50 = 3.07 nM). Additionally, compound 11e had good potential to arrest the HepG2 cell growth at G2/M phase and to induce apoptosis by 49.14% compared to the control cells (9.71%). As well, such compound showed a significant increase in the level of caspase-3 (2.34-fold), caspase-9 (2.34-fold), and BAX (3.14-fold), and a significant decrease in Bcl-2 level (3.13-fold). For in silico studies, the synthesised compounds showed binding mode similar to that of the reference compound (sorafenib).
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- 2021
27. Revealing the Acetylcholinesterase Inhibitory Potential of
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Kolade O, Faloye, Shafi, Mahmud, Emmanuel G, Fakola, Yemisi M, Oyetunde, Sunday J, Fajobi, Jeremiah P, Ugwo, Ayobami J, Olusola, Samson O, Famuyiwa, Oluwabukunmi G, Olajubutu, Temitope I, Oguntade, and Ahmad J, Obaidullah
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The inhibition of acetylcholinesterase plays a vital role in the treatment of Alzheimer disease. This study aimed to explore the acetylcholinesterase inhibition potential of
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- 2022
28. Identification of Zinc-Binding Inhibitors of Matrix Metalloproteinase-9 to Prevent Cancer Through Deep Learning and Molecular Dynamics Simulation Approach
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Shalini Mathpal, Priyanka Sharma, Tushar Joshi, Veena Pande, Shafi Mahmud, Mi-Kyung Jeong, Ahmad J. Obaidullah, Subhash Chandra, and Bonglee Kim
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Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Molecular Biology ,Biochemistry - Abstract
The overexpression of matrix metalloproteinase-9 (MMP-9) is associated with tumor development and angiogenesis, and hence, it has been considered an attractive drug target for anticancer therapy. To assist in drug design endeavors for MMP-9 targets, an in silico study was presented to investigate whether our compounds inhibit MMP-9 by binding to the catalytic domain, similar to their inhibitor or not. For that, in the initial stage, a deep-learning algorithm was used for the predictive modeling of the CHEMBL321 dataset of MMP-9 inhibitors. Several regression models were built and evaluated based on R2, MAE MSE, RMSE, and Loss. The best model was utilized to screen the drug bank database containing 9,102 compounds to seek novel compounds as MMP-9 inhibitors. Then top high score compounds were selected for molecular docking based on the comparison between the score of the reference molecule. Furthermore, molecules having the highest docking scores were selected, and interaction mechanisms with respect to S1 pocket and catalytic zinc ion of these compounds were also discussed. Those compounds, involving binding to the catalytic zinc ion and the S1 pocket of MMP-9, were considered preferentially for molecular dynamics studies (100 ns) and an MM-PBSA (last 30 ns) analysis. Based on the results, we proposed several novel compounds as potential candidates for MMP-9 inhibition and investigated their binding properties with MMP-9. The findings suggested that these compounds may be useful in the design and development of MMP-9 inhibitors in the future.
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- 2022
29. Neuroprotective activity of Ipomoea cairica leaf extract against cadmium chloride-induced biochemical changes in the brain of male Wistar rats
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Omotayo B. Ilesanmi, Temitope Temiloluwa Odewale, Oghenetega J. Avwioroko, Mohammed Alqarni, Ahmad J. Obaidullah, Francis O. Atanu, Toyin Binang, and Gaber El-Saber Batiha
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General Earth and Planetary Sciences ,General Environmental Science - Abstract
Background Exposure to cadmium is implicated in the etiology of some neurodegenerative diseases. Compounds isolated from Ipomoea cairica extract are neuroprotective. However, there is no reported neuroprotective activity of the crude extract of I. cairica (ICE). We investigated the neuroprotective activity of I. cairica extract against cadmium-induced biochemical changes in the brain of male Wistar rats. Thirty-six animals were divided into four groups of 9 animals per group: group I (Control); group II (3.5 mg/kg CdCl2); group III (100 mg/kg ICE + CdCl2); and group IV (250 mg/kg ICE + CdCl2). Animals were pretreated with 100 and 250 mg/kg ICE before co-administration with cadmium chloride. Results CdCl2 treatment caused a significant increase in acetylcholineesterase activity, lipid peroxidation, beta-amyloid aggregation, caspase 3 and 9, p53, and glutamate concentration. In addition, CdCl2 caused a significant decrease in catalase activity, superoxide dismutase, glutathione-S-transferase, Na+/K+ ATPase, and glutamate dehydrogenase. ICE was able to reduce the neuronal damaging effect of CdCl2 by acting as an antioxidant, antiapoptotic, anticholinesterase, and antiexcitotoxicity. Conclusions Our findings show that Ipomoea cairica leaf can be developed and included in the natural product in the prevention of neurodegenerative diseases.
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- 2022
30. Validated Microwell-Based Spectrofluorimetric Method for Quantification of Ravidasvir (New Anti-Chronic Hepatitis C Virus-GT4) in Rat Plasma and Its Application to Pharmacokinetic Study
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Mohamed M. Hefnawy, Ahmad J. Obaidullah, Sherif F. Hammad, Nawaf A. Alsaif, Sara T. Al-Rashood, Mona M. Al-Shehri, Manal A. El-Gendy, Mohammed M. Alanazi, and Mostafa Mohammed
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Male ,Bioanalysis ,Hepatitis C virus ,Pharmaceutical Science ,rat plasma ,medicine.disease_cause ,Antiviral Agents ,Sensitivity and Specificity ,pharmacokinetic study ,chemistry.chemical_compound ,Pharmacokinetics ,Limit of Detection ,Drug Discovery ,medicine ,Animals ,Protein precipitation ,Rats, Wistar ,NS5A ,spectrofluorimetry ,Original Research ,Pharmacology ,Detection limit ,Drug Design, Development and Therapy ,Chromatography ,Reproducibility of Results ,Valine ,Hepatitis C, Chronic ,Ravidasvir ,Rats ,Spectrometry, Fluorescence ,chemistry ,Tolerability ,Area Under Curve ,Benzimidazoles ,ravidasvir - Abstract
Mohamed Hefnawy,1,2 Mona Al-Shehri,1 Sara Al-Rashood,1 Sherif Hammad,3,4 Mohammed Alanazi,1 Nawaf Alsaif,1 Mostafa Mohammed,1,5 Ahmad Obaidullah,1 Manal El-Gendy1 1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 2Department of Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt; 4Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City 21934, Alexandria, Egypt; 5National Organization for Drug Control and Research, Cairo, EgyptCorrespondence: Manal El-GendyDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi ArabiaEmail maelgendy@ksu.edu.saBackground: Ravidasvir (RAV) has been regarded as a potent new NS5A inhibitor with a magnificent safety and tolerability in the management of genotype 4 hepatitis C virus (HCV) patients. Suitable analytical techniques are needed for the measurement of RAV in different biological matrices.Methods: We have developed a fast, sensitive and economical 96-microwell-based spectrofluorimetric technique combined with one-step protein precipitation extraction strategy for the measurement of RAV in rat plasma.Results: Under the optimum conditions, the direct relationship in rat plasma was accomplished between the RAV concentrations and the fluorescence (FL) intensity in a scope of 2.5– 200 ng/mL with 0.9998 and 0.9999 for the quantification and correlation coefficients, respectively. The lower limit of detection (LLOD) was 0.840 ng/mL and this demonstrates the high sensitivity of the proposed assay. The accuracy (RE%) ranged from 95.34% to 102.29%, and the precision (RSD%) was less than 3.59%. The recovery was ranged from 93.12% to 96.26%. The stability of RAV in rat plasma was carried out and established its good stability in the range of room conventional temperature and at long-term stability (− 80°C, 30 days). The developed technique was validated as stated by the United States Food and Drug Administration (US-FDA) guidelines for bioanalytical technique verification.Conclusion: The approved technique was effectively applied for a pharmacokinetic (PK) study after single oral gavage administration of RAV at a dose of 35 mg/kg and it could be presumed that the proposed assay can be applied to clinical trials.Keywords: spectrofluorimetry, ravidasvir, rat plasma, pharmacokinetic study
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- 2020
31. Exploring structure-activity relationship of S-substituted 2-mercaptoquinazolin-4(3H)-one including 4-ethylbenzenesulfonamides as human carbonic anhydrase inhibitors
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Sivia Bua, Alessio Nocentini, Ahmad J. Obaidullah, Hany E. A. Ahmed, Alaa A.-M. Abdel-Aziz, Adel S. El-Azab, Mohamed M. Hefnawy, Nawaf A. Alsaif, and Claudiu T. Supuran
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Gene isoform ,quinazolinone ,Metalloenzyme ,RM1-950 ,Inhibitory postsynaptic potential ,01 natural sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,Carbonic anhydrase ,Drug Discovery ,Structure–activity relationship ,sulphonamide ,Humans ,Carbonic Anhydrase Inhibitors ,Quinazolinone ,molecular docking study ,Carbonic Anhydrases ,Pharmacology ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,selectivity ,General Medicine ,inhibition ,0104 chemical sciences ,Isoenzymes ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Biochemistry ,biology.protein ,Quinazolines ,Therapeutics. Pharmacology ,Selectivity ,Research Paper - Abstract
Inhibitory action of newly synthesised 4-(2-(2-substituted-thio-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides compounds 2–13 against human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII, was evaluated. hCA I was efficiently inhibited by compounds 2–13 with inhibition constants (KIs) ranging from 57.8–740.2 nM. Compounds 2, 3, 4, and 12 showed inhibitory action against hCA II with KIs between 6.4 and 14.2 nM. CA IX exhibited significant sensitivity to inhibition by derivatives 2–13 with KI values ranging from 7.1 to 93.6 nM. Compounds 2, 3, 4, 8, 9, and 12 also exerted potent inhibitory action against hCA XII (KIs ranging from 3.1 to 20.2 nM). Molecular docking studies for the most potent compounds 2 and 3 were conducted to exhibit the binding mode towards hCA isoforms as a promising step for SAR analyses which showed similar interaction with co-crystallized ligands. As such, a subset of these mercaptoquinazolin-4(3H)-one compounds represented interesting leads for developing new efficient and selective carbonic anhydrase inhibitors (CAIs) for the management of a variety of diseases including glaucoma, epilepsy, arthritis and cancer., Graphical Abstract
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- 2020
32. Synthesis, anti-inflammatory, cytotoxic, and COX-1/2 inhibitory activities of cyclic imides bearing 3-benzenesulfonamide, oxime, and β-phenylalanine scaffolds: a molecular docking study
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Adel S. El-Azab, Manal A. El-Gendy, Mohammed M. Alanazi, Abdulrahman A. Almehizia, Hamad M. Alkahtani, Ahmad J. Obaidullah, Alaa A.-M. Abdel-Aziz, Ibrahim A. Al-Suwaidan, and Nawaf A. Alsaif
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Stereochemistry ,medicine.drug_class ,Phenylalanine ,cox-1/2 inhibition ,Antineoplastic Agents ,RM1-950 ,Imides ,Inhibitory postsynaptic potential ,01 natural sciences ,Anti-inflammatory ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Oximes ,Drug Discovery ,medicine ,Animals ,Edema ,Humans ,Cytotoxic T cell ,Cyclooxygenase Inhibitors ,anti-inflammatory activity ,Cell Proliferation ,cytotoxic activity ,Pharmacology ,Sulfonamides ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,molecular docking ,General Medicine ,Oxime ,Rats ,0104 chemical sciences ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Cyclooxygenase 2 ,cyclic imide ,Cyclooxygenase 1 ,Therapeutics. Pharmacology ,Drug Screening Assays, Antitumor ,Research Paper - Abstract
Cyclic imides containing 3-benzenesulfonamide, oxime, and β-phenylalanine derivatives were synthesised and evaluated to elucidate their in vivo anti-inflammatory and ulcerogenic activity and in vitro cytotoxic effects. Most active anti-inflammatory agents were subjected to in vitro COX-1/2 inhibition assay. 3-Benzenesulfonamides (2–4, and 9), oximes (11–13), and β-phenylalanine derivative (18) showed potential anti-inflammatory activities with 71.2–82.9% oedema inhibition relative to celecoxib and diclofenac (85.6 and 83.4%, respectively). Most active cyclic imides 4, 9, 12, 13, and 18 possessed ED50 of 35.4–45.3 mg kg−1 relative to that of celecoxib (34.1 mg kg−1). For the cytotoxic evaluation, the selected derivatives 2–6 and 8 exhibited weak positive cytotoxic effects (PCE = 2/59–5/59) at 10 μM compared to the standard drug, imatinib (PCE = 20/59). Cyclic imides bearing 3-benzenesulfonamide (2–5, and 9), acetophenone oxime (11–14, 18, and 19) exhibited high selectivity against COX-2 with SI > 55.6–333.3 relative to that for celecoxib [SI > 387.6]. β-Phenylalanine derivatives 21–24 and 28 were non-selective towards COX-1/2 isozymes as indicated by their SI of 0.46–0.68.
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- 2020
33. Network Pharmacology- and Molecular Docking-Based Identification of Potential Phytocompounds from Argyreia capitiformis in the Treatment of Inflammation
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Ahmad J. Obaidullah, Mohammed M. Alanazi, Nawaf A. Alsaif, Ashwag S. Alanazi, Hussam Albassam, Alanazi AZ, Osama I. Alwassil, Ali M. Alqahtani, and Abu Montakim Tareq
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Other systems of medicine ,Article Subject ,Complementary and alternative medicine ,RZ201-999 ,Research Article - Abstract
The methanolic extract of Argyreia capitiformis stem was examined for anti-inflammatory activities following network pharmacology analysis and molecular docking study. Based on gas chromatography-mass spectrometry (GC-MS) analysis, 49 compounds were identified from the methanolic extract of A. capitiformis stem. A network pharmacology analysis was conducted against the identified compounds, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology analysis of biological processes and molecular functions were performed. Six proteins (IL1R1, IRAK4, MYD88, TIRAP, TLR4, and TRAF6) were identified from the KEGG pathway analysis and subjected to molecular docking study. Additionally, six best ligand efficiency compounds and positive control (aspirin) from each protein were evaluated for their stability using the molecular dynamics simulation study. Our study suggested that IL1R1, IRAK4, MYD88, TIRAP, TLR4, and TRAF6 proteins may be targeted by compounds in the methanolic extract of A. capitiformis stem to provide anti-inflammatory effects.
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- 2022
34. Molecular Docking and Dynamics Studies to Explore Effective Inhibitory Peptides Against the Spike Receptor Binding Domain of SARS-CoV-2
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Suvro Biswas, Shafi Mahmud, Mohasana Akter Mita, Shamima Afrose, Md. Robiul Hasan, Mst. Sharmin Sultana Shimu, Md. Abu Saleh, Gomaa Mostafa-Hedeab, Mohammed Alqarni, Ahmad J. Obaidullah, and Gaber El-Saber Batiha
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SARS-CoV-2 ,peptide-protein docking ,QH301-705.5 ,peptides ,Biology (General) ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Molecular Biology ,Biochemistry ,molecular dynamics ,RBD - Abstract
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic due to the high transmission and mortality rate of this virus. The world health and economic sectors have been severely affected by this deadly virus, exacerbated by the lack of sufficient efficient vaccines. The design of effective drug candidates and their rapid development is necessary to combat this virus. In this study, we selected 23 antimicrobial peptides from the literature and predicted their structure using PEP-FOLD 3.5. In addition, we docked them to the SARS-CoV-2 spike protein receptor-binding domain (RBD) to study their capability to inhibit the RBD, which plays a significant role in virus binding, fusion and entry into the host cell. We used several docking programs including HDOCK, HPEPDOCK, ClusPro, and HawkDock to calculate the binding energy of the protein-peptide complexes. We identified four peptides with high binding free energy and docking scores. The docking results were further verified by molecular dynamics (MD) simulations to characterize the protein-peptide complexes in terms of their root-mean-square fluctuation (RMSF), root-mean-square deviation (RMSD), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen bond formation. Allergenicity and toxicity predictions suggested that the peptides we identified were non-allergenic and non-toxic. This study suggests that these four antimicrobial peptides could inhibit the RBD of SARS-CoV-2. Future in vitro and in vivo studies are necessary to confirm this.
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- 2022
35. Inhibition of α-Amylase, α-Glucosidase, and Lipase, Intestinal Glucose Absorption, and Antidiabetic Properties by Extracts of Erodium guttatum
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Kaoutar Benrahou, Hanae Naceiri Mrabti, Abdelhakim Bouyahya, Nour Elhouda Daoudi, Mohamed Bnouham, Hicham Mezzour, Shafi Mahmud, Mohammed Merae Alshahrani, Ahmad J. Obaidullah, Yahia Cherrah, and My El Abbes Faouzi
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Complementary and alternative medicine ,Article Subject - Abstract
Erodium guttatum is widely used in traditional medicine to treat various diseases, including diabetes. In this study, we evaluated in vitro inhibitory activity of extracts of E. guttatum on α-amylase, α-glucosidase, and lipase and then studied in vivo using different animal models. The results showed that the aqueous and alcoholic extracts of E. guttatum significantly inhibited digestive enzymes. The extracts of E. guttatum significantly reduced postprandial hyperglycemia after starch loading in normal rats. Additionally, extracts of E. guttatum significantly decrease the intestinal absorption of D-glucose. However, the methanolic extract of E. guttatum showed remarkable antidiabetic activity compared to the aqueous and ethanolic extracts of E. guttatum. In addition, the extracts significantly reduced blood sugar levels in albino mice and hematological and biochemical profiles. Therefore, the results of this study show that the extracts of E. guttatum have antidiabetic effects and could therefore be suggested in the management of type 2 diabetes.
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- 2022
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36. Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment
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Amos Sunday Onikanni, Bashir Lawal, Augustine O Olusola, Janet O Olugbodi, Saidu Sani, Basiru Olaitan Ajiboye, Omotayo B Ilesanmi, Mohammed Alqarni, Gomaa Mostafa-Hedeab, Ahmad J Obaidullah, Gaber El-Saber Batiha, and Alexander TH Wu
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cholinesterase ,antidiabetic ,Sterculia tragacantha ,Immunology ,Immunology and Allergy ,Journal of Inflammation Research ,neurotransmitters ,Original Research ,oxidative stress markers - Abstract
Amos Sunday Onikanni,1â 3,* Bashir Lawal,4,5,* Augustine O Olusola,1 Janet O Olugbodi,6 Saidu Sani,7 Basiru Olaitan Ajiboye,8 Omotayo B Ilesanmi,9 Mohammed Alqarni,10 Gomaa Mostafa-Hedeab,11,12 Ahmad J Obaidullah,13,14 Gaber El-Saber Batiha,15 Alexander TH Wu16â 21 1Toxicology and Environmental Laboratory, Department of Biochemistry, Faculty of Science, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria; 2Biochemistry Unit, Department of Chemical Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria; 3Graduate Institute of Biomedical Science, College of Medicine, China Medical University, Taipei, Taiwan; 4PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, 11031, Taiwan; 5Graduate Institute of Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 6Department of Biochemistry, Bingham University, Karu, Nigeria; 7Department of Biochemistry, Faculty of Biological Science, Alex Ekwueme Federal University Ndufu Alike IkwoD, Abakaliki, Ebonyi State, Nigeria; 8Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Faculty of Science, Federal University, Oye-Ekiti, Ekiti State, Nigeria; 9Department of Biochemistry, Faculty of Science, Federal University Otuoke, Ogbia, Bayelsa State, 23401, Nigeria; 10Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia; 11Pharmacology Department & Health Research Unit, Medical College, Jouf University, Sakakah, Saudi Arabia; 12Pharmacology Department, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt; 13Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 14Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 15Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt; 16The PhD Program of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 17International Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; 18TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan; 19Clinical Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan; 20Taipei Heart Institute, Taipei Medical University, Taipei, 11031, Taiwan; 21Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan*These authors contributed equally to this workCorrespondence: Alexander TH Wu Tel +886 2 2697 2035Email chaw1211@tmu.edu.twBackground: Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant.Methods: The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34± 6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups AâD were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control.Results: The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC50 = 63.03± 2.57 μg/mL), DPPH (117.49± 2.35 μg/mL), FRAP (15.19± 0.98 mmol/100g), TAC (43.38± 0.96 mg/100g), hypoglycaemic effect; α-amylase (IC50 = 77.21± 4.35 μg/mL) and α-glucosidase (IC50 = 443.25± 12.35), and anti-cholinesterase; AChE (IC50 = 113.07± 3.42 μg/mL) and BChE (IC50 = 87.50± 4.32 μg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na+-K+-ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between â 8.0 and â 11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL.Conclusion: The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.Keywords: Sterculia tragacantha, cholinesterase, antidiabetic, neurotransmitters, oxidative stress markers
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- 2021
37. Maternal Transmission of SARS-CoV-2: Safety of Breastfeeding in Infants Born to Infected Mothers
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Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Francis O. Atanu, Mona A. EL-Zamkan, Hassan M. Diab, Ahmed S. Ahmed, Thabat J. Al-Maiahy, Ahmad J. Obaidullah, Sultan Alshehri, Mohammed M. Ghoniem, and Gaber E. Batiha
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pandemic ,infectious disease ,maternal transmission ,Pediatrics, Perinatology and Child Health ,breast milk ,COVID-19 ,Review ,Pediatrics ,RJ1-570 - Abstract
Coronavirus disease 2019 (COVID-19) is a recent epidemic disease caused by severe acute respiratory syndrome virus type 2 (SARS-CoV-2). In pregnancy, SARS-Cov-2 infection creates additional alarm due to concerns regarding the potential for transmission from the mother to the baby during both the antenatal and postpartum times. In general, breastfeeding is seldom disallowed because of infection of the mother. However, there are few exceptions with regards to certain infectious organisms with established transmission evidence from mother to infant and the link of infection of a newborn with significant morbidity and mortality. It is confirmed that pregnant women can become infected with SARS-CoV-2, although the debate on the possible vertical transmission of SARS-CoV-2 infection during pregnancy is still open. In this regard, the literature is still poor. On the contrary, the information on the safety of breastfeeding even during infections seems reassuring when the mother takes the necessary precautions. However, there are still answered questions regarding the precautions to be taken during breastfeeding by COVID-19 patients. This paper reviews the existing answers to these and many other questions. This review therefore presents a summary of the present-day understanding of infection with SARS-CoV-2 and discusses the answers around the maternal transmission of COVID-19 and the potential threat of breastfeeding to babies born to infected pregnant mothers. In conclusion, intrauterine transmission of SARS-CoV-2 infection is less likely to occur during pregnancy. Most studies suggest that COVID-19 is not transmitted through breast milk. Correspondingly, COVID-19-infected neonates might acquire the infection via the respiratory route because of the postnatal contact with the mother rather than during the prenatal period. International organizations encourage breastfeeding regardless of the COVID-19 status of the mother or child as long as proper hygienic and safety measures are adhered to so as to minimize the chance of infant infection by droplets and direct contact with the infected mother. Pasteurized donor human milk or infant formula as supplemental feeding can be quite beneficial in the case of mother–infant separation till breastfeeding is safe.
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- 2021
38. Targeting VEGFR-2 by new quinoxaline derivatives: Design, synthesis, antiproliferative assay, apoptosis induction, and in silico studies
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Abdullah M. Al-Hossaini, Alaa Elwan, Ahmad J. Obaidullah, Hamad M. Alkahtani, Mohammed S Taghour, Nawaf A. Alsaif, Mohammed M. Alanazi, Abdulrahman A Al-Mehizi, and Hazem A. Mahdy
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Sorafenib ,In silico ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,chemistry.chemical_compound ,Inhibitory Concentration 50 ,Mice ,Structure-Activity Relationship ,Quinoxaline ,Quinoxalines ,Drug Discovery ,medicine ,Animals ,Humans ,Computer Simulation ,IC50 ,Hep G2 Cells ,Cell cycle ,Triazoles ,Vascular Endothelial Growth Factor Receptor-2 ,Rats ,Vascular endothelial growth factor ,chemistry ,Toxicity ,MCF-7 Cells ,Female ,medicine.drug - Abstract
Twelve new triazolo[4,3-a]quinoxaline-based compounds are reported as anticancer agents with potential effects against vascular endothelial growth factor receptor-2 (VEGFR-2), using sorafenib as a reference molecule. With sorafenib as the positive control, the antiproliferative effects of the synthesized compounds against MCF-7 and HepG2 cells, as well as their VEGFR-2-inhibitory activities, were assessed. The most powerful VEGFR-2 inhibitor was compound 14a, which had an IC50 value of 3.2 nM, which is very close to that of sorafenib (IC50 = 3.12 nM). Furthermore, compounds 14c and 15d showed potential inhibitory activity against VEGFR-2, with IC50 values of 4.8 and 5.4 nM, respectively. Compound 14a caused apoptosis in HepG2 cells and stopped the cell cycle at the G2/M phase. In HepG2 cells, it also increased the levels of the proteases caspase-3 and caspase-9, as well as the Bax/Bcl-2 ratio. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) and toxicity experiments revealed that the synthesized agents had acceptable drug-likeness.
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- 2021
39. Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
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Mohammed H. Alqarni, Shafi Mahmud, Boris Davy Bekono, Oyenike Idayat Bello, Kolade Olatubosun Faloye, Onikepe Deborah Owoseeni, Emmanuel Gabriel Fakola, Mohammed Merae Alshahrani, Oluwabukunmi Grace Olajubutu, Marcus Durojaye Ayoola, Ahmad J. Obaidullah, and Ahmed Abdullah Al Awadh
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Stereochemistry ,Allosteric regulation ,prenylated flavonoids ,Pharmaceutical Science ,Enzyme Activators ,Organic chemistry ,Article ,Analytical Chemistry ,Molecular dynamics ,QD241-441 ,Prenylation ,Catalytic Domain ,Drug Discovery ,Glucokinase ,glucokinase activators ,Humans ,Physical and Theoretical Chemistry ,density functional theory ,chemistry.chemical_classification ,Flavonoids ,Virtual screening ,biology ,Active site ,molecular docking ,In vitro ,Molecular Docking Simulation ,molecular dynamics simulation ,ADMET ,Enzyme ,chemistry ,Chemistry (miscellaneous) ,biology.protein ,Molecular Medicine - Abstract
Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.
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- 2021
40. Empagliflozin adjunct with metformin for the inhibition of hepatocellular carcinoma progression: Emerging approach for new application
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Noha A. Amin, Ahmad J. Obaidullah, Sameh Saber, Mahmoud E. Youssef, Eslam E. Abd El-Fattah, Mohammed Alqarni, Eman El-Ahwany, Mohamed Ali Etman, Mohamed Awad Shahien, Marwa A. Abd-Eldayem, Hanan Eissa, Gaber El-Saber Batiha, Amir Mohamed Abdelhamid, Mohamed M.Y. Kaddah, and Ahmed Gaafar Ahmed Gaafar
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Carcinoma, Hepatocellular ,endocrine system diseases ,Angiogenesis ,Hepatocellular carcinoma ,Apoptosis ,RM1-950 ,Pharmacology ,Hypoglycemia ,Metastasis ,Mice ,Glucosides ,Empagliflozin ,Autophagy ,Medicine ,Animals ,Hypoglycemic Agents ,Benzhydryl Compounds ,Sodium-Glucose Transporter 2 Inhibitors ,Neovascularization, Pathologic ,business.industry ,Liver Neoplasms ,NF-kappa B ,AMPK ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,MAP Kinase Kinase Kinases ,Emagliflozin/metformin ,Metformin ,Disease Progression ,Therapeutics. Pharmacology ,business ,medicine.drug ,Signal Transduction - Abstract
Hepatocellular carcinoma (HCC) is on the rise worldwide, and its incidence in diabetic patients is two to three times that of non-diabetics. Current therapeutic options fail to provide considerable survival benefits to patients with HCC. There is a strong possibility that the FDA-approved antidiabetic combination of empagliflozin and metformin could show complementary effects to control HCC progression. However, their multitarget effects have not yet been studied on HCC development. Therefore, the present study aims to evaluate the antitumorigenic activity of this combination in non-diabetic mice with diethylnitrosamine-induced HCC. Empagliflozin/metformin combination prolonged survival and improved histological features of mice livers. Additionally, Empagliflozin/metformin showed anti-inflammatory potential and relieved oxidative stress. On the one hand these effects are likely attributed to the ability of metformin to inactivate NF-κB in an AMPK-dependent mechanism and on the other hand to the ability of the empagliflozin to inhibit the MAPKs, p38 and ERK1/2. Empagliflozin also showed a less robust effect on AMPK than that of metformin. Moreover, empagliflozin enhanced the autophagy inducing activity of metformin. Furthermore, empagliflozin/metformin exhibited increased apoptotic potential. Consequently, empagliflozin augmented the antitumorigenic function of metformin by exerting better control of angiogenesis, and metastasis. To conclude, our findings suggest empagliflozin as an ideal adjunct to metformin for the inhibition of HCC progression. In addition, since the incidence of hypoglycemia is minimal due to insulin-independent mechanism of action of both treatments, empagliflozin/metformin could be a promising therapeutic modality for the management of diabetic patients with HCC; and even non diabetic ones.
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- 2021
41. New quinoxaline-based VEGFR-2 inhibitors: design, synthesis, and antiproliferative evaluation with
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Mohammed M, Alanazi, Hazem, Elkady, Nawaf A, Alsaif, Ahmad J, Obaidullah, Hamad M, Alkahtani, Manal M, Alanazi, Madhawi A, Alharbi, Ibrahim H, Eissa, and Mohammed A, Dahab
- Abstract
A new series of 3-methylquinoxaline-based derivatives having the same essential pharmacophoric features as VEGFR-2 inhibitors have been synthesized and evaluated for their antiproliferative activities against two human cancer cell lines, MCF-7 and HepG-2. Compounds 15b and 17b demonstrated a significant antiproliferative effect with IC
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- 2021
42. Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and
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Mohammed M, Alanazi, Elwan, Alaa, Nawaf A, Alsaif, Ahmad J, Obaidullah, Hamad M, Alkahtani, Abdulrahman A, Al-Mehizia, Sultan M, Alsubaie, Mohammed S, Taghour, and Ibrahim H, Eissa
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3-methylquinoxalin-2(1H)-one ,Cell Cycle ,apoptosis ,Antineoplastic Agents ,Vascular Endothelial Growth Factor Receptor-2 ,Rats ,Molecular Docking Simulation ,Structure-Activity Relationship ,Anticancer ,3-methylquinoxaline-2-thiol ,in silico studies ,VEGFR-2 inhibitors ,Cell Line, Tumor ,Quinoxalines ,Drug Discovery ,Animals ,Humans ,Computer Simulation ,Drug Screening Assays, Antitumor ,Cell Proliferation ,Research Article ,Research Paper - Abstract
There is an urgent need to design new anticancer agents that can prevent cancer cell proliferation even with minimal side effects. Accordingly, two new series of 3-methylquinoxalin-2(1H)-one and 3-methylquinoxaline-2-thiol derivatives were designed to act as VEGFR-2 inhibitors. The designed derivatives were synthesised and evaluated in vitro as cytotoxic agents against two human cancer cell lines namely, HepG-2 and MCF-7. Also, the synthesised derivatives were assessed for their VEGFR-2inhibitory effect. The most promising member 11e were further investigated to reach a valuable insight about its apoptotic effect through cell cycle and apoptosis analyses. Moreover, deep investigations were carried out for compound 11e using western-plot analyses to detect its effect against some apoptotic and apoptotic parameters including caspase-9, caspase-3, BAX, and Bcl-2. Many in silico investigations including docking, ADMET, toxicity studies were performed to predict binding affinity, pharmacokinetic, drug likeness, and toxicity of the synthesised compounds. The results revealed that compounds 11e, 11g, 12e, 12g, and 12k exhibited promising cytotoxic activities (IC50 range is 2.1 − 9.8 µM), comparing to sorafenib (IC50 = 3.4 and 2.2 µM against MCF-7 and HepG2, respectively). Moreover, 11b, 11f, 11g, 12e, 12f, 12g, and 12k showed the highest VEGFR-2 inhibitory activities (IC50 range is 2.9 − 5.4 µM), comparing to sorafenib (IC50 = 3.07 nM). Additionally, compound 11e had good potential to arrest the HepG2 cell growth at G2/M phase and to induce apoptosis by 49.14% compared to the control cells (9.71%). As well, such compound showed a significant increase in the level of caspase-3 (2.34-fold), caspase-9 (2.34-fold), and BAX (3.14-fold), and a significant decrease in Bcl-2 level (3.13-fold). For in silico studies, the synthesised compounds showed binding mode similar to that of the reference compound (sorafenib).
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- 2021
43. Design, synthesis and molecular docking of new [1,2,4] triazolo[4,3-a]quinoxaline derivatives as anticancer agents targeting VEGFR-2 kinase
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Nawaf A, Alsaif, Alaa, Elwan, Mohammed M, Alanazi, Ahmad J, Obaidullah, Wael A, Alanazi, Abdullah F, Alasmari, Hussam, Albassam, Hazem A, Mahdy, and Mohammed S, Taghour
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Vascular Endothelial Growth Factor A ,Molecular Structure ,Antineoplastic Agents ,Sorafenib ,Vascular Endothelial Growth Factor Receptor-2 ,Molecular Docking Simulation ,Structure-Activity Relationship ,Drug Design ,Quinoxalines ,MCF-7 Cells ,Humans ,Drug Screening Assays, Antitumor ,Protein Kinase Inhibitors ,Cell Proliferation - Abstract
Vascular endothelial growth factor receptor-2 (VEGFR-2) is critically involved in cancer angiogenesis. Blocking of VEGFR-2 signaling pathway proved effective suppression of tumor growth. Accordingly, two series of new triazoloquinoxaline-based derivatives were designed and synthesized as VEGFR-2 inhibitors. All in vitro cytotoxic activities of the synthesized compounds were evaluated against two human cancer cell lines (MCF-7 and HepG2). To confirm the potential mechanism of cytotoxicity, enzymatic assays against VEGFR-2 were estimated for all the target compounds. The results of VEGFR-2 inhibitory activity and cytotoxicity were in high correlation. Compound 22a exhibited the highest cytotoxic effect with IC
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- 2021
44. AKT-AMPKα-mTOR-dependent HIF-1α Activation is a New Therapeutic Target for Cancer Treatment: A Novel Approach to Repositioning the Antidiabetic Drug Sitagliptin for the Management of Hepatocellular Carcinoma
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Eslam E. Abd El-Fattah, Sameh Saber, Mahmoud E. Youssef, Hanan Eissa, Eman El-Ahwany, Noha A. Amin, Mohammed Alqarni, Gaber El-Saber Batiha, Ahmad J. Obaidullah, Mohamed M.Y. Kaddah, Ahmed Gaafar Ahmed Gaafar, Ahmed A.E. Mourad, Gomaa Mostafa-Hedeab, and Amir Mohamed Abdelhamid
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Pharmacology ,angiogenesis ,Akt ,AMPKα ,mTOR ,HIF-1α ,Pharmacology (medical) ,Therapeutics. Pharmacology ,RM1-950 ,hepatocellular carcinoma ,MAPK ,sitagliptin ,Original Research - Abstract
HIF-1α is a key factor promoting the development of hepatocellular carcinoma (HCC). As well, AKT-AMPKα-mTOR signaling is a promising target for cancer therapy. Yet, the AKT-AMPKα-mTOR-dependent activation of HIF-1α has not been studied in livers with HCC. In addition, the mechanisms underlying the potential antineoplastic effects of sitagliptin (STGPT), an antidiabetic agent, have not yet been elucidated. For that purpose, the N-nitrosodiethylamine (NDEA)-induced HCC mouse model was used in the present study using a dose of 100 mg/kg/week, i.p., for 8 weeks. NDEA-induced HCC mice received STGPT 20, 40, or 80 mg/kg starting on day 61 up to day 120. The present study revealed that STGPT inhibited HIF-1α activation via the interference with the AKT-AMPKα-mTOR axis and the interruption of IKKβ, P38α, and ERK1/2 signals as well. Accordingly, STGPT prolonged the survival, restored the histological features and improved liver function. Additionally, STGPT inhibited angiogenesis, as revealed by a significant downregulation in the VEGF and mRNA expression of CD309 with concomitant inhibition of tissue invasion was evident by an increased ratio of TIMP-1/MMP-2. STGPT exhibited apoptotic stimulatory effect as indicated upon calculating the BCL-2/Bax ratio and by the gene expression of p53. The decrease in AFP and liver index calculation, gene expression of Ki-67 confirmed the antiproliferative activity of STGPT. The anti-inflammatory potential was revealed by the decreased TNF-α level and the downregulation of MCP-1 gene expression. Moreover, an antifibrotic potential was supported by lower levels of TGF-β. These effects appear to be GLP1R-independent. The present study provides a potential basis for repurposing STGPT for the inhibition of HCC progression. Since STGPT is unlikely to cause hypoglycemia, it may be promising as monotherapy or adjuvant therapy to treat diabetic or even normoglycemic patients with HCC.
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- 2021
45. Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3
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Nawaf A, Alsaif, Mohammed S, Taghour, Mohammed M, Alanazi, Ahmad J, Obaidullah, Abdulrahman A, Al-Mehizia, Manal M, Alanazi, Saleh, Aldawas, Alaa, Elwan, and Hazem, Elkady
- Subjects
Dose-Response Relationship, Drug ,Molecular Structure ,apoptosis ,Antineoplastic Agents ,Apoptosis ,molecular docking ,Vascular Endothelial Growth Factor Receptor-2 ,Structure-Activity Relationship ,VEGFR-2 ,Anticancer ,Quinoxalines ,Drug Discovery ,bis([1,2,4]triazolo)[4,3-a:3',4'-c]quinoxaline ,Humans ,Drug Screening Assays, Antitumor ,Protein Kinase Inhibitors ,Cell Proliferation ,Research Article ,Research Paper - Abstract
Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC50 values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC50 values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).
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- 2021
46. Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2
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Abdulrahman A. Almehizia, Hussam Albassam, Saad Ahmed Sami, Nawaf A. Alsaif, Ali Alqahtani, Shafi Mahmud, Ahmad J. Obaidullah, Mohammed M. Alanazi, and Talha Bin Emran
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0301 basic medicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,viruses ,General Chemical Engineering ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,fungi ,General Chemistry ,Multi epitope ,Biology ,Virology ,respiratory tract diseases ,body regions ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,skin and connective tissue diseases - Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a contagious respiratory tract infection that has become a global burden since the end of 2019. Notably, fewer patients infected with SARS-CoV-2 progress from acute disease onset to death compared with the progression rate associated with two other coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Several research organizations and pharmaceutical industries have attempted to develop successful vaccine candidates for the prevention of COVID-19. However, increasing evidence indicates that the SARS-CoV-2 genome undergoes frequent mutation; thus, an adequate analysis of the viral strain remains necessary to construct effective vaccines. The current study attempted to design a multi-epitope vaccine by utilizing an approach based on the SARS-CoV-2 structural proteins. We predicted the antigenic T- and B-lymphocyte responses to four structural proteins after screening all structural proteins according to specific characteristics. The predicted epitopes were combined using suitable adjuvants and linkers, and a secondary structure profile indicated that the vaccine shared similar properties with the native protein. Importantly, the molecular docking analysis and molecular dynamics simulations revealed that the constructed vaccine possessed a high affinity for toll-like receptor 4 (TLR4). In addition, multiple descriptors were obtained from the simulation trajectories, including the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (
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- 2021
47. Development and Validation of a Chiral Liquid Chromatographic Assay for Enantiomeric Separation and Quantification of Verapamil in Rat Plasma: Stereoselective Pharmacokinetic Application
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Abdulmalik Bin Saleh Al-Tamimi, Abdulrhman A. Al-Majed, Ahmad J. Obaidullah, Abdullah M. Al-Hossaini, Nasser Algrain, Mohamed M. Hefnawy, Mostafa Mohammed, Haitham AlRabiah, and Yousef A. Bin Jardan
- Subjects
Administration, Oral ,Pharmaceutical Science ,02 engineering and technology ,rat plasma ,01 natural sciences ,High-performance liquid chromatography ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,chemistry.chemical_compound ,lcsh:Organic chemistry ,Drug Discovery ,verapamil enantiomers ,Trifluoroacetic acid ,Animals ,Solid phase extraction ,Rats, Wistar ,Physical and Theoretical Chemistry ,chiral HPLC ,Triethylamine ,Chromatography ,core–shell chiral column ,010401 analytical chemistry ,Organic Chemistry ,Reproducibility of Results ,Stereoisomerism ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Chiral column chromatography ,Verapamil ,chemistry ,Chemistry (miscellaneous) ,Molecular Medicine ,Biological Assay ,Stereoselectivity ,stereoselective pharmacokinetics ,Enantiomer ,0210 nano-technology ,Isopropyl ,Chromatography, Liquid - Abstract
A novel, fast and sensitive enantioselective HPLC assay with a new core–shell isopropyl carbamate cyclofructan 6 (superficially porous particle, SPP) chiral column (LarihcShell-P, LSP) was developed and validated for the enantiomeric separation and quantification of verapamil (VER) in rat plasma. The polar organic mobile phase composed of acetonitrile/methanol/trifluoroacetic acid/triethylamine (98:2:0.05: 0.025, v/v/v/v) and a flow rate of 0.5 mL/min was applied. Fluorescence detection set at excitation/emission wavelengths 280/313 nm was used and the whole analysis process was within 3.5 min, which is 10-fold lower than the previous reported HPLC methods in the literature. Propranolol was selected as the internal standard. The S-(−)- and R-(+)-VER enantiomers with the IS were extracted from rat plasma by utilizing Waters Oasis HLB C18 solid phase extraction cartridges without interference from endogenous compounds. The developed assay was validated following the US-FDA guidelines over the concentration range of 1–450 ng/mL (r2 ≥ 0.997) for each enantiomer (plasma) and the lower limit of quantification was 1 ng/mL for both isomers. The intra- and inter-day precisions were not more than 11.6% and the recoveries of S-(−)- and R-(+)-VER at all quality control levels ranged from 92.3% to 98.2%. The developed approach was successfully applied to the stereoselective pharmacokinetic study of VER enantiomers after oral administration of 10 mg/kg racemic VER to Wistar rats. It was found that S-(−)-VER established higher Cmax and area under the concentration-time curve (AUC) values than the R-(+)-enantiomer. The newly developed approach is the first chiral HPLC for the enantiomeric separation and quantification of verapamil utilizing a core–shell isopropyl carbamate cyclofructan 6 chiral column in rat plasma within 3.5 min after solid phase extraction (SPE).
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- 2021
48. Deeper Insights on Cnesmone javanica Blume Leaves Extract: Chemical Profiles, Biological Attributes, Network Pharmacology and Molecular Docking
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Ahmad J. Obaidullah, Mohammed M. Alanazi, Omer I. Fantoukh, Abu Montakim Tareq, Saad Ahmed Sami, Talha Bin Emran, Nawaf A. Alsaif, Wael A. Mahdi, and Ali Alqahtani
- Subjects
Elevated plus maze ,medicine.drug_class ,Plant Science ,Pharmacology ,Anxiolytic ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cnesmone javanica ,medicine ,network pharmacology ,GC–MS ,Phenols ,Ecology, Evolution, Behavior and Systematics ,Serotonin transporter ,030304 developmental biology ,0303 health sciences ,antidepressant ,Ecology ,biology ,Chemistry ,Botany ,molecular docking ,Terpenoid ,QK1-989 ,biology.protein ,Antidepressant ,Gas chromatography–mass spectrometry ,Diazepam ,030217 neurology & neurosurgery ,anxiolytic ,medicine.drug - Abstract
This study assessed the anxiolytic and antidepressant activities of a methanol leaves extract of Cnesmone javanica (CV) in Swiss albino mice. The study found a significant increase in the percentage of time spent in the open arms of an elevated plus maze and in the incidence of head dipping in hole-board tests following the administration of 400 mg/kg of CV or 1 mg/kg diazepam. Moreover, a significant (p <, 0.001) dose-dependent reduction was observed in the immobility time following CV (200 and 400 mg/kg) and fluoxetine (20 mg/kg) administration for forced swimming and tail suspension tests. Gas chromatography–mass spectroscopy (GC–MS) analysis identified 62 compounds in CV, consisting primarily of phenols, terpenoids, esters, and other organic compounds. A molecular docking study was performed to assess the anxiolytic and antidepressant effects of 45 selected compounds against human serotonin transporter and potassium channels receptors. Network pharmacology was performed to predict the pathways involved in these neuropharmacological effects. Overall, CV demonstrated significant and dose-dependent anxiolytic and antidepressant effects due to the presence of several bioactive phytoconstituents, which should be further explored using more advanced and in-depth mechanistic research.
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- 2021
49. Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study
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Ahmad J. Obaidullah, Ibrahim A. Al-Suwaidan, Abdulrahman M. Al-Obaid, Adel S. El-Azab, Alaa A.-M. Abdel-Aziz, and Nawaf A. Alsaif
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Scaffold ,egfr inhibition ,her2 inhibition ,cox-2 inhibition ,Hydrazone ,Antineoplastic Agents ,Apoptosis ,RM1-950 ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Humans ,antitumor activity ,Cell Proliferation ,cell cycle analysis ,Pharmacology ,Antitumor activity ,chemistry.chemical_classification ,Sulfonamides ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,hydrazones synthesis ,Egfr inhibition ,Cell Cycle ,Hydrazones ,food and beverages ,molecular docking ,General Medicine ,Combinatorial chemistry ,Molecular Docking Simulation ,Cell cycle analysis ,enzymatic assay ,Therapeutics. Pharmacology ,Drug Screening Assays, Antitumor ,Pharmacophore ,Research Article ,Research Paper - Abstract
Hydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4–24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with a positive cytotoxic effect (PCE) of 52/59, 27/59, 59/59, and 59/59, respectively, while compounds 5, 10, 14, 15, 18, and 19 had a moderate antitumor activity with a PCE of 11/59–14/59. Compound 20 was the most active and had a mean 50% cell growth inhibition (GI50) of 0.26 µM. Compounds 9 and 20 showed the highest inhibitory activity against COX-2, with a half-maximal inhibitory concentration (IC50) of 2.97 and 6.94 μM, respectively. Compounds 16 and 20 significantly inhibited EGFR (IC50 = 0.2 and 0.19 μM, respectively) and HER2 (IC50 = 0.13 and 0.07 μM, respectively). Molecular docking studies of derivatives 9, 16, and 20 into the binding sites of COX-2, EGFR, and HER2 were carried out to explore the interaction mode and the structural requirements for antitumor activity., Graphical Abstract Compound 20 (MG_MID = 0.26 µM) is nearly 65-fold more potent than celecoxib (MG_MID = 17.5 µM), 3-fold more potent than 5-Fu (MG_MID = 0.90 µM), 30-fold more potent than erlotinib (MG_MID = 7.68 µM), and 9-fold more potent than gefitinib (MG_MID = 2.1 µM) and sorafenib (MG_MID = 2.33 µM).
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- 2021
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- View/download PDF
50. Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers
- Author
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Nawaf A. Alsaif, Ahmad J. Obaidullah, Alaa Elwan, Saleh Aldawas, Mohammed S Taghour, Mohammed M. Alanazi, Manal M. Alanazi, Abdulrahman A. Almehizia, and Hazem Elkady
- Subjects
Sorafenib ,Stereochemistry ,vegfr-2 ,RM1-950 ,anticancer ,01 natural sciences ,chemistry.chemical_compound ,Quinoxaline ,Drug Discovery ,medicine ,Cytotoxic T cell ,Inducer ,IC50 ,Pharmacology ,010405 organic chemistry ,Chemistry ,apoptosis ,molecular docking ,General Medicine ,In vitro ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Cell culture ,Apoptosis ,bis([1,2,4]triazolo)[4,3-a:3',4'-c]quinoxaline ,Therapeutics. Pharmacology ,medicine.drug - Abstract
Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC50 values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC50 values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).
- Published
- 2021
- Full Text
- View/download PDF
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