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Ahmed M Naglah,1,2 Gaber O Moustafa,2 Ahmed A Elhenawy,3,4 Marwa M Mounier,5 Heba El-Sayed,6 Mohamed A Al-Omar,1 Abdulrahman A Almehizia,1,7 Mashooq A Bhat7 1Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 2Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Cairo, Egypt; 3Chemistry Department, Faculty of Science, Al-Azhar University (Boys’Branch), Cairo, Egypt; 4Chemistry Department, Faculty of Science, Albaha University, Al Baha, Saudi Arabia; 5Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt; 6Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, Egypt; 7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Gaber O Moustafa; Ahmed Elhenawy Tel +201003123355; +966599044526Email gosman79@gmail.com; elhenawy_sci@hotmail.comPurpose: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents.Introduction: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates.Methods: The main backbone structure for the novel synthesized linear peptide is Nα-1, 3-benzenedicarbonyl-bis-(Amino acids)-X, ( 3– 11). A computational docking study against DNA gyrase was performed to formulate a mode of action of the small compounds as antimicrobial agents.Results: The peptide-bearing methionine-ester ( 4) exhibited potent antimicrobial activity compared to the other synthesized compounds, while, peptide ( 8), which had methionine-hydrazide fragment was the most potent as antifungal agent against Aspergillus niger with 100% inhibition percent. Compounds ( 6 and 7) showed the highest potency against breast human tumor cell line “MCF-7” with 95.1% and 79.8% of cell inhibition, respectively. The nine compounds possessed weak to moderate antiproliferative effect over colon tumor cell line. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues. In silico ADMET study also evaluated and suggested that these compounds had promising oral bioavailability features.Conclusion: The tested compounds need further modification to have significant antimicrobial and antitumor efficacy compared to the reference drugs.Keywords: anticancer, antimicrobial activity, linear-peptides, Nα-1, 3-benzenedicarbonyl-bis-peptides, molecular docking

Mashooq Ahmad Bhat,1 Mohamed A Al-Omar,1 Azmat Ali Khan,1 Amer M Alanazi,1 Ahmed M Naglah2,31Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 2Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 3Peptide Chemistry Department, Chemical Industries Research Division, National Research, Centre, Cairo, EgyptPurpose: To evaluate the antihepatotoxic activity of dihydropyrimidinone derivative linked with 1,4-benzodioxane.Methods: A series of novel dihydropyrimidinone derivatives linked with 1,4-benzodioxane moiety were synthesized in good yield. Modern spectroscopic techniques and elemental analysis were used for the identification of the synthesized compounds. The hepatoprotective properties of compound 2, 4-(4-nitrophenyl)-5-(2,3-dihydro-1,4-benzodioxin-6-ylcarbonyl)-3,4-dihydropyrimidin-2(1H)-one, was evaluated in a carbon tetrachloride (CCl4)-induced hepatotoxicity rat model.Results: Administration of compound 2 prior to CCl4 exposure produced a dose-dependent decrease in the levels of elevated biochemical parameters compared with the standard drug silymarin. CCl4 induced oxidative stress, increased lipid profile, and decreased high-density lipoprotein (HDL) levels. Compound 2 (20 mg/kg) significantly reduced the lipid profile and significantly improved HDL levels in a dose-dependent manner. CCl4 treatment increased malondialdehyde (MDA) level and decreased nonprotein thiol (NP-SH) and total protein (TP) in liver tissues. Pretreatment of rats with compound 2 (20 mg/kg) decreased MDA level and increased NP-SH and TP in liver tissues. Histopathological examination of liver tissues also confirmed the hepatoprotective activity of compound 2.Conclusion: These results demonstrate the antihepatotoxic activity of compound 2 in CCl4-induced hepatotoxicity model.Keywords: antihepatotoxic activity, dihydropyrimidinone, 14-benzodioxane, carbon tetrachloride, silymarin

Ahmed M Naglah,1,2 Moamen S Refat,3,4 Mohamed A Al-Omar,1 Mashooq A Bhat,5 Hamad M AlKahtani,5 Asma S Al-Wasidi6 1Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 2Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Cairo 12622, Egypt; 3Chemistry Department, Faculty of Science, Taif University, Taif 21974, Saudi Arabia; 4Department of Chemistry, Faculty of Science, Port Said University, Port Said, Egypt; 5Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 6Department of Chemistry, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia Background: This study aimed to design a compound with folic acid (FAH2) and vanadyl (IV) for use in the treatment of diabetes.Materials and methods: A novel vanadyl (IV) FAH2 complex was synthesized and characterized [(FA2-)(VO2+)]·3H2O. The speculated structure of this folate complex was determined using physicochemical techniques including microanalytical analysis, conductivity studies, spectroscopic examination, magnetic measurements, thermogravimetric analyses, and morphological X-ray powder diffraction, and scanning and transmission electron microscopies. The anti-diabetic therapeutic potential of the complexes was tested in a 30-day streptozotocin-induced diabetes rat model.Results: The conductivity test of the complex implied electrolyte behavior. The spectroscopic assessments of the isolated dark yellow solid complex revealed that FAH2 acts as a bidentate ligand. The coordination process with two vanadyl (IV) ions occurred through the deprotonation of both carboxyl groups of FAH2 in a regular square pyramid arrangement at a 2(FA)2-: 2(VO)2+ molar ratio. XRD, SEM, and TEM analyses revealed the complex crystalline nature of the complex. Treating diabetic rats with vanadyl (IV) FAH2 complex significantly improved many biological parameters relevant to diabetes pathology with minimal toxicity.Conclusion: The data generated in this study indicate that the synthesized vanadyl (IV) folate complex acts as a model of anti-diabetic agent. Keywords: diabetes, vanadyl, folic acid, spectroscopic, streptozotocin, vitamin B9

Increasing fertility rates have become one of the factors that concern all people in the world. Therefore, the study aims to use two mutated strains of probiotics enriched with selenium (PSe40/60/1 and BSe50/20/1) to improve fertility. Thirty Swiss albino male mice were divided into three groups; control, LP + S was given Lactobacillus plantarum PSe40/60/1 plus selenium, and BL + S was given Bifidobacterium longum BSe50/20/1 plus selenium. Free testosterone, LH, and FSH were measured in serum by biochemical analysis. Testicular tissues were examined by histopathological analysis. The count and motility of sperm, and sperm abnormalities were determined by microscopic examination. The method of qRT-PCR was used to detect gene expression of Tspyl1, Hsd3b6, and Star genes. The biochemical results showed that serum content of free testosterone (FT) hormone had significantly increase in the BL + S and LP + S groups compared with control. Levels of LH and FSH hormones were the highest in the BL + S group. The treated groups showed all developmental stages of spermatogenesis, including spermatogenesis, spermatocytes, and seminiferous tubule spermatids, as well as intact Sertoli cells and Leydig cells without changes. When compared to the control group, sperm count and motility increased in the BL + S group, while sperm abnormalities decreased. The expression of Tspyl1 gene in testicular tissues decreased in the LP + S and BL + S groups, while the expression of Star and Hsd3b6 genes was higher in the BL + S group and lower in the LP + S group compared with the control group. Therefore, Bifidobacterium longum BSe50/20/1 enriched with selenium could be useful in enhancing male fertility., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background : Alzheimer's disease (AD) is characterized by cholinergic dysfunction, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) critical for improving cholinergic neurotransmission. However, the development of effective dual inhibitors remains challenging. Objective : This study aims to synthesize and evaluate novel pyridazine-containing compounds as potential dual inhibitors of AChE and BuChE for AD treatment. Methods : Ten novel pyridazine-containing compounds were synthesized and characterized using IR, 1 H NMR, and 13 C NMR. The inhibitory activities against AChE and BuChE were assessed in vitro, and pharmacokinetic properties were explored through in silico ADME studies. Molecular dynamics simulations were performed for the most active compound. Results : Compound 5 was the most potent inhibitor, with IC 50 values of 0.26 µM for AChE and 0.19 µM for BuChE, outperforming rivastigmine and tacrine, and showing competitive results with donepezil. Docking studies revealed a binding affinity of -10.21 kcal/mol to AChE and -13.84 kcal/mol to BuChE, with stable interactions confirmed by molecular dynamics simulations. In silico ADME studies identified favorable pharmacokinetic properties for compounds 5 , 8 , and 9 , with Compound 5 showing the best activity. Conclusions : Compound 5 demonstrates strong potential as a dual cholinesterase inhibitor for Alzheimer's disease, supported by both in vitro and in silico analyses. These findings provide a basis for further optimization and development of these novel inhibitors.

Copper-Vit B 3 MOF was successfully prepared by efficient and eco hydrothermal method. The prepared MOF was characterized as a tetragonal crystal copper-MOF nanoparticles by FTIR, SEM, TEM, EDX and XRD. The prepared nanoparticles were used as an effective, inexpensive and low-toxic catalyst in the one-pot synthesis of some new benzoxanthenone derivatives. As example 4-(9,9-dimethyl-11-oxo-8,10,11,12-tetrahydro-9 H -benzo[ a ]xanthen-12-yl)phenyl benzoate (4h) was synthesized in high yield 92%. The MOF catalyst's role is activating the nucleophilic attack by increasing the carbonyl polarization, and this generally improves the reaction time, which ranges between 20-60 minutes and products' yields ranging between 80-92%. Prepared compounds (4a-4j) undergo molecular docking scanning as Helicobacter pylori type II dehydroquinase inhibitors, and the data obtained showed that there are three promises of the prepared compounds 4d, 4e, 4h and 4j compared with amoxicillin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a - f , 6a - f , and 7a - f , to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer's, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a - f , 6a - f , and 7a - f showed that the six pyrazole-based Schiff bases 5a , 5d , 5e , 5f , 7a , and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d , 5e , and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a , 5d , 5e , 5f , 7a , and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7 - 9, 11 - 13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy ( 1 H and 13 C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

There is a need for new pharmaceutical discoveries from bioactive nitrogenous derivatives due to the emergence of scourges, numerous pandemics, and diverse health problems. In this context, pyrazolo[1,5- a ]pyrimidine derivatives 12a and 12b were synthesized and screened to evaluate their biological potentials in vitro as antioxidants, anti-diabetics, anti-Alzheimer's, anti-arthritics, and anti-cancer agents. Additionally, the computational pharmacokinetic and toxicity properties of the two pyrazolo[1,5- a ]pyrimidines 12a and 12b were calculated and analyzed. The preliminary studies and results of this work represent the initial steps toward more advanced studies and define the bioactive chemical structure of pyrazolo[1,5- a ]pyrimidine derivatives with the goal of exploring new drugs to address numerous health problems., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

A screen-printed potentiometric sensor for the erythromycin macrolide antibiotic (ERY) that is affordable, highly selective, and sensitive is made, described, and used for drug monitoring. Two circular carbon dots with a diameter of 4 mm make up the sensor. Multiwalled carbon nanotubes and polyaniline (f-MWCNTs/PANi) nanocomposites are used to change one carbon spot, which is then used as an ion-to-electron transfer material. Ag/AgCl is applied to the other spot, which is then used as a reference electrode. A solid-state polyvinyl butyral (PVB) is placed onto the second carbon spot to work as a reference electrode, and an ERY molecularly imprinted drug polymer (MIP) is coated onto the f-MWCNTs/PANi-containing strip to serve as a drug identification sensing material. Chronopotentiometry (CP) is used to analyze the integrated sensor's performance characteristics. It is confirmed that f-MWCNTs/PANi has an increased impact on the potential stability as well as the sensing membrane's interfacial double-layer capacitance. At a detection limit of 9.6 ± 0.4 × 10 -7 M, the developed sensor exhibits a Nernstian slope of 54.0 ± 0.5 mV per decade ( R 2 = 0.9994) over the linear range of 4.6 × 10 -6 to 1.0 × 10 -3 M. When exposed to different related substances such azithromycin, clarithromycin, dirithromycin, paracetamol, and ascorbic acid, the sensor exhibits excellent selectivity. For the direct potentiometric determination of ERY in some pharmaceutical formulations and in samples of spiked human urine, the assay method has been validated and shown to be adequate. The obtained recovery ranges from 93.0 ± 0.5 to 104.3 ± 0.7 of the nominal or spiked concentration, with a mean relative standard deviation of ±0.6%. Due to the near closeness of the responsive membrane and the liquid junction, the use of all-solid-state electrodes coupled with a planar disposable platform enables applications with a minimum sample volume. The effectiveness of the suggested sensor in a complex urine matrix points to its use in hospitals for quick overdose patient detection as well as for quality control/quality assurance tests in the pharmaceutical sector., Competing Interests: The authors declare that there are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

In medicine, barbiturates are a class of depressive medications used as hypnotics, anticonvulsants, and anxiolytics. For the treatment of specific forms of epilepsy and seizures in young children in underdeveloped countries, the World Health Organization recommends phenobarbital (PBAR), a barbiturate drug. This review describes the fabrication and characterization of a paper-based analytical apparatus for phenobarbital detection that is straightforward, affordable, portable, and disposable. All of the solid-state ion-selective electrodes (ISEs) for PBAR as well as a Ag/AgCl reference electrode were constructed and optimized on a nonconductive paper substrate. Using carbon nanotube ink, the sensors were made to function as an ion-to-electron transducer and to make the paper conductive. A suitable polymeric membrane is drop-cast onto the surface of the carbon ink orifice. The pyrido-tetrapeptide and pyrido-hexapeptide derivatives, which were recently synthesized, functioned as distinct ionophores in the PBAR-membrane sensor, enabling its detection. With a detection limit of 5.0 × 10 -7 M, the manufactured analytical device demonstrated a Nernstian response to PBAR anions in 50 mM phosphate buffer, pH 8.5, over a linear range of 1.0 × 10 -6 to 1.0 × 10 -3 M. The PBAR-based sensors showed quick (less than 5 s) response times for PBAR ion detection. The modified separate solution method was utilized to evaluate the selectivity pattern of these novel ionophores with respect to PBAR ions in comparison to other common anions. The analytical instrument that was exhibited on paper had good precision both within and between days. The suggested technology assisted in the detection of trace amounts of PBAR in real pharmaceutical samples. A comparison was made between the data acquired using the HPLC reference method and the information obtained by the recommended potentiometric approach. The described paper-based analytical device may be a good choice for point-of-care PBAR determination because it is cheap and easy to find and can self-pump (especially when combined with potentiometric detection)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1 H -pyrazolo[3,4- c ]pyridazin-3-amine ( 4 ) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4 . Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4- c ]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics.

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14 days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Isoflavenes have received the greatest research attention among the many groups of phytoestrogens. In this study, various isoflavene-based Mannich bases were selected for their theoretical studies. The purpose of this research was to discover the binding potential of all the designated Mannich bases acting as inhibitors against cancerous proteins EGFR, cMet, hTrkA, and HER2 (PDB codes: 5GTY, 3RHK, 6PL2, and 7JXH, respectively). For their virtual screening, DFT calculations and molecular docking studies were undertaken using in silico software. Docking studies predicted that ligands 5 and 15 exhibited the highest docking score by forming hydrogen bonds within the active pocket of protein 6PL2, ligands 1 and 15 both with protein 3RHK, and 7JXH, 12, and 17 with protein 5GTY. Rendering to the trends in polarizability and dipole moment, the energy gap values (0.2175 eV, 0.2106 eV) for the firm conformers of Mannich bases (1 and 4) replicate the increase in bioactivity and chemical reactivity. The energy gap values (0.2214 eV and 0.2172 eV) of benzoxazine-substituted isoflavene-based Mannich bases (9 and 10) reflect the increase in chemical potential due to the most stable conformational arrangements. The energy gap values (0.2188 eV and 0.2181 eV) of isoflavenes with tertiary amine-based Mannich bases (14 and 17) reflect the increase in chemical reactivity and bioactivity due to the most stable conformational arrangements. ADME was also employed to explore the pharmacokinetic properties of targeted moieties. This study revealed that these ligands have a strong potential to be used as drugs for cancer treatment.

Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC 50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC 50 9.45±0.05 μM followed by 3 e (IC 50 22.52±0.15 μM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Herein, we described for the first time, an efficient biogenic synthesis of APTs-AgNPs using acid protease from Melilotus indicus leaf extract. The acid protease (APTs) has an essential role in the stabilization, reduction, and capping of APTs-AgNPs. The crystalline nature, size, and surface morphology of APTs-AgNPs were examined using different techniques such as XRD, UV, FTIR, SEM, EDS, HRTEM, and DLS analysis. The generated APTs-AgNPs demonstrated notable performance as dual functionality (photocatalyst and antibacterial disinfection). By destroying 91 % of methylene blue (MB) in <90 min of exposure, APTs-AgNPs demonstrated remarkable photocatalytic activity. APTs-AgNPs also showed remarkable stability as a photocatalyst after five test cycles. Furthermore, the APTs-AgNPs was found to be a potent antibacterial agent with inhibition zones of 30(±0.5 mm), 27(±0.4 mm), 16(±0.1 mm), and 19(±0.7 mm) against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, respectively, under both light and dark conditions. Furthermore, APTs-AgNPs effectively scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, demonstrating their potent antioxidant activity. The outcomes of this study thus demonstrates the dual functionality of APTs-AgNPs produced using the biogenic approach method as a photocatalyst and an antibacterial agent for effective microbial and environmental control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Potentilla nepalensis Hook is a perennial Himalayan medicinal herb of the Rosaceae family. The present study aimed to evaluate biological activities such as the antioxidant, antibacterial, and anticancer activities of roots and shoots of P. nepalensis and its synergistic antibacterial activity with antibacterial drugs. Folin-Ciocalteau and aluminium chloride methods were used for the calculation of total phenolic (TPC) and flavonoid content (TFC). A DPPH radical scavenging assay and broth dilution method were used for the determination of the antioxidant and antibacterial activity of the root and shoot extracts of P. nepalensis . Cytotoxic activity was determined using a colorimetric MTT assay. Further, phytochemical characterization of the root and shoot extracts was performed using the Gas chromatography-mass spectrophotometry (GC-MS) method. The TPC and TFC were found to be higher in the methanolic root extract of P. nepalensis . The methanolic shoot extract of P. nepalensis showed good antioxidant activity, while then-hexane root extract of P. nepalensis showed strong cytotoxic activity against tested SK-MEL-28 cells. Subsequently, in silico molecular docking studies of the identified bioactive compounds predicted potential anticancer properties. This study can lead to the production of new herbal medicines for various diseases employing P. nepalensis , leading to the creation of new medications.

Introduction: Cadmium (Cd) is a highly toxic heavy metal that can be found everywhere in the environment and can have harmful effects on both human and animal health. Pinostrobin (PSB) is a bioactive natural flavonoid isolated from Boesenbergia rotunda with several pharmacological properties, such as antiinflammatory, anticancer, antioxidant, and antiviral. This investigation was intended to assess the therapeutic potential of PSB against Cd-induced kidney damage in rats., Methods: In total, 48 Sprague Dawley rats were divided into four groups: a control, a Cd (5 mg/kg), a Cd + PSB group (5 mg/kg Cd and 10 mg/kg PSB), and a PSB group (10 mg/kg) that received supplementation for 30 days., Results: Exposure to Cd led to a decrease in the activities of catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX), whereas levels of reactive oxygen species (ROS) and malondialdehyde (MDA) increased. Cd exposure also caused a substantial increase in urea, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and creatinine levels. Moreover, a noticeable decline was noticed in creatinine clearance. Moreover, Cd exposure considerably increased the levels of inflammatory indices, including interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), nuclear factor kappa-B (NF-kB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) activity. Cd treatment decreased the expression of the antiapoptotic markers (Bcl-2) while increasing the expression of apoptotic markers (Bax and Caspase-3). Furthermore, Cd treatment substantially reduced the TCA cycle enzyme activity, such as alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase. Moreover, mitochondrial electron transport chain enzymes, succinatedehydrogenase, NADH dehydrogenase, cytochrome c-oxidase, and coenzyme Q-cytochrome reductase activities were also decreased following Cd exposure. PSB administration substantially reduced the mitochondrial membrane potential while inducing significant histological damage. However, PSB treatment significantly reduced Cd-mediated renal damage in rats., Conclusion: Thus, the present investigation discovered that PSB has ameliorative potential against Cd-induced renal dysfunction in rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ijaz, Shahzadi, Hamza, Azmat, Anwar, Afsar, Shafique, Bhat, Naglah, Al-Omar and Razak.)

One of the cardiac biomarkers, myoglobin (Mb), is important in the rapid identification of cardio-vascular disorders. Therefore, point-of-care monitoring is essential. Pursuing this goal, a robust, reliable, and affordable paper-based analytical apparatus for potentiometric sensing has been developed and characterized. The molecular imprint technique was used to create a customized biomimetic antibody for myoglobin (Mb) on the surface of carboxylated multiwalled carbon nanotubes (MWCNT-COOH). This was accomplished by attaching Mb to carboxylated MWCNTs' surfaces and then filling the empty spaces through the mild polymerization of acrylamide in N , N -methylenebisacrylamide and ammonium persulphate. The modification of the MWCNTs' surface was verified by SEM and FTIR analysis. A hydrophobic paper substrate coated with fluorinated alkyl silane (CF 3 (CF 2 ) 7 CH 2 CH 2 SiCl 3 , CF 10 ) has been coupled with a printed all-solid-state Ag/AgCl reference electrode. The presented sensors showed a linear range of 5.0 × 10 -8 to 1.0 × 10 -4 M with a potentiometric slope of -57.1 ± 0.3 mV decade -1 ( R 2 = 0.9998) and a detection limit of 28 nM at pH 4. Compared to creatinine, sucrose, fructose, galactose, sodium glutamate, thiamine, alanine, ammonium, uric acid, albumin, glutamine, guanine, troponine T, and glucose, the sensor showed good selectivity for Mb. It demonstrated a good recovery for the detection of Mb in several fake serum samples (93.0-103.3%), with an average relative standard deviation of 4.5%. The current approach might be viewed as a potentially fruitful analytical tool for obtaining disposable, cost-effective paper-based potentiometric sensing devices. These types of analytical devices can be potentially manufacturable at large scales in clinical analysis., Competing Interests: The authors declare that there are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

5-bromopyridine-2,3-diamine reacted with benzaldehyde to afford the corresponding 6-Bromo-2-phenyl-3H-imidazo[4,5-b]pyridine ( 1 ). The reaction of the latter compound ( 1 ) with a series of halogenated derivatives under conditions of phase transfer catalysis solid-liquid (CTP) allows the isolation of the expected regioisomers compounds ( 2 - 8 ). The alkylation reaction of (1) gives, each time, two regioisomers, N3 and N4; in the case of ethyl bromoactate, the reaction gives, at the same time, the three N1, N3 and N4 regioisomers. The structures of synthesized compounds were elucidated on the basis of different spectral data ( 1 H NMR, 13 C NMR), X-Ray diffraction and theoretical study using the DFT method, and confirmed for each compound. Hirshfeld surface analysis was used to determine the intermolecular interactions responsible for the stabilization of the molecule. Density functional theory was used to optimize the compounds, and the HOMO-LUMO energy gap was calculated, which was used to examine the inter/intra molecular charge transfer. The molecular electrostatic potential map was calculated to investigate the reactive sites that were present in the molecule. In order to determine the potential mode of interactions with DHFR active sites, the three N1, N3 and N4 regioisomers were further subjected to molecular docking study. The results confirmed that these analogs adopted numerous important interactions, with the amino acid of the enzyme being targeted. Thus, the most docking efficient molecules, 2 and 4 , were tested in vitro for their antibacterial activity against Gram-positive bacteria ( Bacillus cereus ) and Gram-negative bacteria ( Escherichia coli ). Gram-positive bacteria were more sensitive to the action of these compounds compared to the Gram-negative, which were much more resistant.

A thermostable acid protease from M. indicus leaves was purified 10-fold using a 4-step protocol. We were able to isolate a purified protease fraction with a molecular weight of 50 kDa and exhibited maximal protease activity at pH 4.0 and 40 °C. Structural analysis revealed that the protease is monomeric and non-glycosylated. The addition of epoxy monocarboxylic acid, iodoacetic acid, and dimethyl sulfoxide significantly reduced protease activity while dramatically increasing the inhibition of Mn 2+ , Fe 2+ , and Cu 2+ . The activation energy of the hydrolysis reaction (33.33 kJ mol -1 ) and activation energy (E d  = 105 kJ mol -1 ), the standard enthalpy variation of reversible protease unfolding (2.58 kJ/mol) were calculated after activity measurements at various temperatures. Thermal inactivation of the pure enzyme followed first-order kinetics. The half-life (t 1/2 ) of the pure enzyme at 50 °C, 60 °C, and 70 °C was 385, 231, and 154 min, respectively. Thermodynamic parameters (entropy and enthalpy) suggested that the protease was highly thermostable. This is the first report on the thermodynamic parameters of proteases produced by M. indicus. The novel protease appears to be particularly thermostable and may be important for industrial applications based on these thermodynamic properties., Competing Interests: Declaration of competing interest The author has no conflict of interest exits in the submission of this manuscript and the authors have complied with journal ethical requirements. Moreover, manuscript is approved by all authors as well as all the authorities acknowledged for publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Terminalia arjuna possesses significant cardioprotective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna . Spectroscopic characterization identified one of them as a new flavonoid " Terminalone A ( 1 )" and two known flavonoids i.e., 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one ( 2 ) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one ( 3 ). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH radical scavenging) potential for all the three compounds 1 - 3 where the compound 1 showed strong antibacterial and antioxidant activity.

Alzheimer's disease remains a global health challenge and an unmet need requiring innovative approaches to discover new drugs. The current study aimed to investigate the inhibitory activity of Albizia lucidior and Albizia procera leaves against acetylcholinesterase enzyme in vitro and explore their chemical compositions. Metabolic profiling of the bioactive plant, A. lucidior , via UHPLC/MS/MS-based Molecular Networking highlighted the richness of its ethanolic extract with budmunchiamine alkaloids, fourteen budmunchiamine alkaloids as well as four new putative ones were tentatively identified for the first time in A. lucidior . Pursuing these alkaloids in the fractions of A. lucidior extract via molecular networking revealed that alkaloids were mainly concentrated in the ethyl acetate fraction. In agreement, the alkaloid-rich fraction showed the most promising anticholinesterase activity (IC 50 5.26 µg/mL) versus the ethanolic extract and ethyl acetate fraction of A. lucidior (IC 50 24.89 and 6.90 µg/mL, respectively), compared to donepezil (IC 50 3.90 µg/mL). Furthermore, deep in silico studies of tentatively identified alkaloids of A. lucidior were performed. Notably, normethyl budmunchiamine K revealed superior stability and receptor binding affinity compared to the two used references: donepezil and the co-crystallized inhibitor (MF2 700). This was concluded based on molecular docking, molecular dynamics simulations and molecular mechanics generalized born/solvent accessibility (MM-GBSA) calculations.

Caffeine is a psychoactive drug that is administered as a class II psychotropic substance. It is also considered a component of analgesics and cold medicines. Excessive intake of caffeine may lead to severe health damage or drug addiction problems. The assessment of normal caffeine consumption from abusive use is not conclusive, and the cut-off value for biological samples has not been established. Herein, new cost-effective and robust all-solid-state platforms based on potentiometric transduction were fabricated and successfully utilized for caffeine assessment. The platforms were modified with reduced graphene oxide (rGO). Tailored caffeine-imprinted polymeric beads (MIPs) based on methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were prepared, characterized, and used as recognition receptors in the presented potentiometric sensing devices. In 50 mM MES buffer, the sensors exhibited a slope response of 51.2 ± 0.9 mV/decade (n = 6, R2 = 0.997) over the linear range of 4.5 × 10−6−1.0 × 10−3 M with a detection limit of 3.0 × 10−6 M. They exhibited fast detection of caffeinium ions with less than 5 s response time (<5 s). The behavior of the presented sensors towards caffeinium ions over many common organic and inorganic cations was evaluated using the modified separate solution method (MSSM). Inter-day and intra-day precision for the presented analytical device was also evaluated. Successful applications of the presented caffeine sensors for caffeine determination in commercial tea and coffee and different pharmaceutical formulations were carried out. The data obtained were compared with those obtained by the standard liquid chromatographic approach. The presented analytical device can be considered an attractive tool for caffeine determination because of its affordability and vast availability, particularly when combined with potentiometric detection.

Novel cost-effective screen-printed potentiometric platforms for simple, fast, and accurate assessment of Fluoxetine (FLX) were designed and characterized. The potentiometric platforms integrate both the FLX sensor and the reference Ag/AgCl electrode. The sensors were based on the use of 4'-nitrobenzo-15-crown-5 (ionophore I), dibenzo-18-crown-6 (ionophore II), and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) (ionophore III) as neutral carriers within a plasticized PVC matrix. Multiwalled carbon nanotubes (MWCNTs) were used as a lipophilic ion-to-electron transducing material and sodium tetrakis [3,5-bis(trifluoromethyl)phenyl] borate (NaTFPB) was used as an anionic excluder. The presented platforms revealed near-Nernstian potentiometric response with slopes of 56.2 ± 0.8, 56.3 ± 1.7 and 64.4 ± 0.2 mV/decade and detection limits of 5.2 × 10 -6 , 4.7 × 10 -6 and 2.0 × 10 -7 M in 10 mM Tris buffer solution, pH 7 for sensors based on ionophore I, II, and III, respectively. All measurements were carried out in 10 mM tris buffer solution at pH 7.0. The interfacial capacitance before and after insertion of the MWCNTs layer was evaluated for the presented sensors using the reverse-current chronopotentiometry. The sensors were introduced for successful determination of FLX drug in different pharmaceutical dosage forms. The results were compared with those obtained by the standard HPLC method. Recovery values were calculated after spiking fixed concentrations of FLX in different serum samples. The presented platforms can be potentially manufacturable at large scales and provide a portable, rapid, disposable, and cost-effective analytical tool for measuring FLX.

Enasidenib (EDB) is a new therapeutic agent for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. This research aimed at utilizing experimental and theoretical approaches to characterize the binding mechanism between EDB and human serum albumin (HSA). Formation of an EDB-HSA static complex was demonstrated by quenching of the HSA intrinsic fluorescence by EDB. Using well known mathematical relations (e.g. Stern-Volmer and Lineweaver-Burk equations), the recorded EDB-HSA fluorescence data were interpreted and revealed binding constants in the magnitude order of 10 4 M -1 for the different investigated temperatures. These determined results were taken into further mathematical calculations to reveal the thermodynamic properties of EDB-HSA binding. Results demonstrated that spontaneous EDB and HSA binding takes place led by electrostatic forces. Computational docking studies have further confirmed the latter finding showing that EDB fits into the HSA Sudlow site I. Molecular dynamic simulation was performed to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (R g ) and hydrogen bond parameters for the EDB-HSA complex., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel series of benzothiazole-based derivatives linked to various amino acids and their corresponding ethyl ester analogues were prepared and were initially evaluated for their anticancer activity againstMCF-7 and HepG-2 and were further assessed as VEGFR-2 inhibitors. All the newly synthesized benzothiazole derivatives showed promising cytotoxic activities against the tested cell lines. Derivatives exhibited potent cytotoxic and VEGFR-2 inhibitory activities were then evaluated further as anticancer agents against the resistant MDA-MB-231 and as EGFR inhibitors. The carboxylic acid derivatives 10-12 and their ester analogues 21-23 displayed the highest anticancer activities with IC 50 of 0.73-0.89 µM, against MCF-7 and IC 50 of 2.54-2.80 µM, against HepG-2; compared to doxorubicin (IC 50  = 1.13 and 2.75 µM, respectively); also they showed safety towards the normal cell line, the ethyl ester derivatives 21-23 showed a potent activity against the resistant MDA-MB-231 cell line with IC 50 of 5.45-7.28 µM, relative to doxorubicin (IC 50  = 7.46 µM) surpassing their carboxylic acid analogues 10-12 (IC 50 of 8.88-11.02 µM). Furthermore, the promising derivatives 10-12 and 21-23 displayed promising VEGFR-2 inhibitory activity (IC 50  = 0.15-0.19 µM) comparable to that of sorafenib (IC 50  = 0.12 µM). Against EGFR, the ethyl ester derivatives 21-23 showed superior inhibitory activity relative to the used reference standard, erlotinib, with IC 50 of 0.11-0.16 vs. 0.18 µM, respectively. The QSAR study revealed that the molecular bulkiness and molecular partial charge distribution govern the kinase inhibition potency in this series. Furthermore, the molecular docking study in VEGFR-2 active site showed that the novel synthesized benzothiazole derivatives adopted the common binding pattern of type II PK inhibitors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The rapid spread of bacterial infection caused by Staphylococcus aureus has become a problem to public health despite the presence of past trials devoted to controlling the infection. Thus, the current study aimed to explore the chemical composition of the extract of endophytic fungus Aspergillus fumigatus , isolated from Albizia lucidior leaves, and investigate the antimicrobial activity of isolated metabolites and their probable mode of actions. The chemical investigation of the fungal extract via UPLC/MS/MS led to the identification of at least forty-two metabolites, as well as the isolation and complete characterization of eight reported metabolites. The antibacterial activities of isolated metabolites were assessed against S. aureus using agar disc diffusion and microplate dilution methods. Compounds ergosterol, helvolic acid and monomethyl sulochrin-4-sulphate showed minimal inhibitory concentration (MIC) values of 15.63, 1.95 and 3.90 µg/mL, respectively, compared to ciprofloxacin. We also report the inhibitory activity of the fungal extract on DNA gyrase and topoisomerase IV, which led us to perform molecular docking using the three most active compounds isolated from the extract against both enzymes. These active compounds had the required structural features for S. aureus DNA gyrase and topoisomerase IV inhibition, evidenced via molecular docking.

All-solid state screen-printed electrodes were fabricated for chlorogenic acid (CGA) detection. The screen-printed platforms were modified with multi-walled carbon nanotubes (MWCNTs) to work as a lipophilic solid-contact transducer. The sensing-membrane was plasticized with a suitable solvent mediator and incorporating [Ni II (bathophenanthroline) 3 ][CGA] 2 complex as a sensory material. In a 30 mM phosphate solution (buffer, pH 6), the sensor revealed a Nernstian-response towards CGA ions with a slope of -55.1 ± 1.1 ( r 2 = 0.9997) over the linear range 1.0 × 10 -7 to 1.0 × 10 -3 (0.035-354.31 μg mL -1 ) with a detection limit 7.0 × 10 -8 M (24.8 ng mL -1 ). It revealed a stable potentiometric response with excellent reproducibility and enhanced selectivity over several common ions. Short-term potential stability and the interfacial sensor capacitance was estimated using both electrochemical-impedance spectroscopy (EIS) and chronopotentiometry techniques. The presented electrochemical platform revealed the merits of design simplicity, ease of miniaturization, good potential-stability, and cost-effectiveness. It is successfully applied to CGA determination in different coffee beans extracts and juice samples. The data obtained were compared with those obtained by liquid chromatography reference method (HPLC)., Competing Interests: The authors declare that there are no conflicts of interest. All authors have approved the manuscript and agree with the submission to your esteemed journal., (This journal is © The Royal Society of Chemistry.)

Glycyrrhetinic acid (GA) is one of many interesting pentacyclic triterpenoids showing significant anticancer activity by triggering apoptosis in tumor cell lines. This study deals with the design and synthesis of new glycyrrhetinic acid (GA)-amino acid peptides and peptide ester derivatives. The structures of the new derivatives were established through various spectral and microanalytical data. The novel compounds were screened for their in vitro cytotoxic activity. The evaluation results showed that the new peptides produced promising cytotoxic activity against the human breast MCF-7 cancer cell line while comparing to doxorubicin. On the other hand, only compounds 3 , 5 , and 7 produced potent activity against human colon HCT-116 cancer cell line. The human liver cancer (HepG-2) cell line represented a higher sensitivity to peptide 7 (IC 50 ; 3.30 μg/mL), while it appeared insensitive to the rest of the tested peptides. Furthermore, compounds 1 , 3 , and 5 exhibited a promising safety profile against human normal skin fibroblasts cell line BJ-1. In order to investigate the mode of action, compound 5 was selected as a representative example to study its in vitro effect against the apoptotic parameters and Bax/BCL-2/p53/caspase-7/caspase-3/tubulin, and DNA fragmentation to investigate beta (TUBb). Additionally, all the new analogues were subjected to antimicrobial assay against a panel of Gram-positive and Gram-negative bacteria and the yeast candida Albicans. All the tested GA analogues 1 - 8 exhibited more antibacterial effect against Micrococcus Luteus than gentamicin, but they exhibited moderate antimicrobial activity against the tested bacterial and yeast strains. Molecular docking studies were also simulated for compound 5 to give better rationalization and put insight to the features of its structure.

A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d , 3e , 3f , and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5-15.10 µg/mL and 0.26-14.92 µg/mL, respectively. The compounds 3e , 3f , and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1 H NMR and 13 C NMR analysis.

Purpose: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents., Introduction: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates., Methods: The main backbone structure for the novel synthesized linear peptide is Nα-1, 3-benzenedicarbonyl-bis-(Amino acids)-X, ( 3-11 ). A computational docking study against DNA gyrase was performed to formulate a mode of action of the small compounds as antimicrobial agents., Results: The peptide-bearing methionine-ester ( 4 ) exhibited potent antimicrobial activity compared to the other synthesized compounds, while, peptide ( 8 ), which had methionine-hydrazide fragment was the most potent as antifungal agent against Aspergillus niger with 100% inhibition percent. Compounds ( 6 and 7 ) showed the highest potency against breast human tumor cell line "MCF-7" with 95.1% and 79.8% of cell inhibition, respectively. The nine compounds possessed weak to moderate antiproliferative effect over colon tumor cell line. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues. In silico ADMET study also evaluated and suggested that these compounds had promising oral bioavailability features., Conclusion: The tested compounds need further modification to have significant antimicrobial and antitumor efficacy compared to the reference drugs., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Naglah et al.)

A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[ g ]quinazolines ( 1 - 17 ) were synthesized, characterized, and evaluated in vitro for their antiangiogenesis VEGFR-2-targeting, antiproliferative, and antiapoptotic activities against breast MCF-7 and liver HepG2 cells. Flow cytometry was used to determine cancer-cell cycle distributions, and apoptosis was detected using annexin-V-FITC (V) and propidium iodide (PI) dyes. Fluorescence microscopy, in combination with Hoechst staining was used to detect DNA fragmentation. Most of the tested benzo[ g ]quinazolines demonstrated promising activity (IC 50 = 8.8 ± 0.5-10.9 ± 0.9 μM) and (IC 50 = 26.0 ± 2.5-40.4 ± 4.1 μM) against MCF-7 and HepG2, respectively. Doxorubicin was used as a reference drug. Compounds 13 - 15 showed the highest activity against both cancer cell lines. Differential effects were detected by cell-cycle analysis, indicating similarities in the actions of 13 and 14 against both MCF7 and HepG2, involving the targeting of G1 and S phases, respectively. Compound 15 showed similar indices against both cells, indicating that its cytotoxicity toward the examined cancer cells could be unselective. Interestingly, 14 and 15 showed the highest apoptosis (30.76% and 25.30%, respectively) against MCF-7. The DNA fragmentation results agreed well with the apoptosis detected by flow cytometry. In terms of antiangiogenesis activity, as derived from VEGFR-2 inhibition, 13 and 15 were comparable to sorafenib and effected 1.5- and 1.4-fold inhibition relative to the standard sorafenib. A docking study was conducted to investigate the interaction between the synthesized benzo[ g ]quinazolines and the ATP-binding site within the catalytic domain of VEGFR-2.

A new series of N'-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1 H -inden-3-yl) acetohydrazide derivatives (1 - 25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised compounds were evaluated for antioxidant activity by DPPH method. Compounds 7 (R = 3-methoxyphenyl), 3 (R = 4-dimethylaminophenyl) and 23 (R = 2,4,5-trimethoxy phenyl) substitutions were found to be having highly potent antioxidant activity. Compound 3 , with para dimethylaminophenyl substitution was found to be having highest antioxidant activity. It was further evaluated in vivo for various analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibitory activity in different animal models. Lead compound 3 was found to be significant anti-inflammatory and analgesic agent. It was also evaluated for ulcerogenic activity and demonstrated significant ulcerogenic reduction activity in ethanol and indomethacin model. The LD 50 of compound 3 was found to be 131 mg/kg. The animals treated with compound 3 prior to cisplatin treatment resulted in a significant reduction in COX-2 protein expression when compared to cisplatin-treated group. Sulindac derivative with para dimethylaminophenyl substitution was found to be the most potent antioxidant, anti-inflammatory and analgesic agent as well as with significant gastric sparing activity as compared to standard drug sulindac. Compound 3 significantly downregulated liver tissue COX-2 gene expression.

Thirteen 4-hydrazinobenzoic acid derivatives were elaborated and characterized by spectral analyses (NMR and MS). Evaluation of their in vitro cytotoxic activity showed that some of the targets demonstrated potent inhibitory effects against HCT-116 and MCF-7 cancer cells. The IC 50 values ranged between 21.3 ± 4.1 and 28.3 ± 5.1 µM, respectively, whereas those of doxorubicin (reference drug) ranged between 22.6 ± 3.9 and 19.7 ± 3.1 µM, respectively. The active targets 6, 7 and 9 exhibited very weak cytotoxicity on normal cells (RPE-1) and showed higher IC 50 values against HCT-116 and MCF-7 cells in comparison to doxorubicin. Furthermore, compounds 7, 9 and 10 inhibited the proliferation of MCF-7 by the induction of apoptosis. The bioassay results in the regression plots generated in 3D QSAR models were in agreement and correlated with the anticancer results of the target molecules. The 4-hydazinobenzoic acid derivatives can be used as cornerstones for further structural modifications as future anticancer agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Within a series of dipeptide derivatives ( 5 - 11 ), compound 4 was refluxed with d-glucose, d-xylose, acetylacetone, diethylmalonate, carbon disulfide, ethyl cyanoacetate, and ethyl acetoacetate which yielded 5 - 11 , respectively. The candidates 5 - 11 were characterized and their biological activities were evaluated where they showed different anti-microbial inhibitory activities based on the type of pathogenic microorganisms. Moreover, to understand modes of binding, molecular docking was used of Nicotinoylglycine derivatives with the active site of the penicillin-binding protein 3 (PBP3) and sterol 14-alpha demethylase's (CYP51), and the results, which were achieved via covalent and non-covalent docking, were harmonized with the biological activity results. Therefore, it was extrapolated that compounds 4 , 7 , 8 , 9 , and 10 had good potential to inhibit sterol 14-alpha demethylase and penicillin-binding protein 3; consequently, these compounds are possibly suitable for the development of a novel antibacterial and antifungal therapeutic drug. In addition, in silico properties of absorption, distribution, metabolism, and excretion (ADME) indicated drug likeness with low to very low oral absorption in most compounds, and undefined blood-brain barrier permeability in all compounds. Furthermore, toxicity (TOPKAT) prediction showed probability values for all carcinogenicity models were medium to pretty low for all compounds.

A search for potent antitubercular agents prompted us to design and synthesize sulfamethaoxazole incorporated 4-thiazolidinone hybrids ( 7a - l ) by using a cyclocondensation reaction between 4-amino- N -(5-methylisoxazol-3-yl)benzenesulfonamide ( 4 ), aryl aldehyde ( 5a - l ), and mercapto acetic acid ( 6 ) resulting in good to excellent yields. All the newly synthesized 4-thiazolidinone derivatives were screened for their in vitro antitubercular activity against M. Bovis BCG and M. tuberculosis H37Ra ( MTB) strains. The compounds 7d , 7g , 7i , 7k , and 7l revealed promising antimycobacterial activity against M. Bovis and MTB strains with IC 90 values in the range of 0.058-0.22 and 0.43-5.31 µg/mL, respectively. The most active compounds were also evaluated for their cytotoxicity against MCF-7, HCT 116, and A549 cell lines and were found to be non-cytotoxic. Moreover, the synthesized compounds were also analyzed for ADME (absorption, distribution, metabolism, and excretion) properties and showed potential as good oral drug candidates.

A series of Bis -pyrazole Schiff bases ( 6a - d and 7a - d ) and mono-pyrazole Schiff bases ( 8a - d and 9a - d ) were designed and synthesized through the reaction of 5-aminopyrazoles 1a - d with aldehydes 2 - 5 using mild reaction condition with a good yield percentage. The chemical structure of newly formed Schiff bases tethered pyrazole core was confirmed based on spectral and experimental data. All the newly formed pyrazole Schiff bases were evaluated against eight pathogens (Gram-positive, Gram-negative, and fungi). The result exhibited that, most of them have good and broad activities. Among those, only six Schiff bases ( 6b , 7b , 7c , 8a , 8d , and 9b ) displayed MIC values (0.97-62.5 µg/mL) compared to Tetracycline (15.62-62.5 µg/mL) and Amphotericin B (15.62-31.25 µg/mL), MBC values (1.94-87.5 µg/mL) and selectivity to tumor cell than normal cells. Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH 2 ) and piperidinyl core. Furthermore, the most potent one exhibited broad activity depending on both MIC and MBC values. Moreover, to study the mechanism of these pyrazole Schiff bases, two active Schiff bases 8a and 9b from six derivatives were introduced to study the enzyme assay as dihydrofolate reductase (DHFR) on E. coli organism and DNA gyrase with two different organisms, S. aureus and B. subtilis , to determine the inhibitory activities with lower values in the case of DNA gyrase ( 8a and 9b ) or nearly as DHFR compound 9b , while pyrazole 8a showed excellent inhibitory against all enzyme assay. The molecular docking study against dihydrofolate reductase and DNA gyrase were performed to study the binding between active site in the pocket with the two Schiff bases ( 8a and 9b ) that exhibited good binding affinity with different bond types as H-bonding, aren-aren, and arene-cation interaction as well as study the physicochemical and pharmacokinetic properties of the two active Schiff bases 8a and 9b .

A new six intraperitoneal injections insulin-mimetic vanadyl(IV) compounds [(VO)(FA)(AA n )] (where n = 1-6: AA 1 = isoleucine, AA 2 = threonine, AA 3 = proline, AA 4 = phenylalanine, AA 5 = lysine, and AA 6 = glutamine) were synthesized by the chemical reactions between folic acid (FA), VOSO 4 , and amino acids (AA n ) with equal molar ratio 1:1:1 in neutralized media. These complexes were characterized by elemental analysis and estimation of vanadyl(IV) metal ions. The thermal stability behavior of these complexes was studied by TG-DTG-DTA analyses. The structures of these complexes were elucidated by spectroscopic methods like infrared, electron spin resonance (ESR), and solid reflectance spectroscopes. The powder X-ray diffraction (XRD) study suggested the crystalline nature of the complexes. Magnetic moments and electronic spectra revealed the square-pyramid geometrical structure of the complexes. The conductivity results refereed that all synthesized vanadyl(IV) complexes were of a non-electrolyte behavior. The infrared spectra assignments of these complexes revealed that the FAH 2 and AA n chelates act as a bidentate ligation. The chelation towards vanadyl (IV) ions existed via deprotonation of one of the carboxylic groups of FAH 2 drug ligand, and so amino acids act as bidentate ligands via N-amino and O-carboxylate groups. Both scanning and transmission electron microscope (SEM and TEM) techniques were used to investigate the surface morphology. The main task of this research is the aim of designing a new insulin alternative antidiabetic drug agent. The antidiabetic efficiency of these complexes was evaluated in streptozotocin-induced diabetic male albino rats. Liver and kidney functions, insulin and blood glucose levels, lipid profile, and superoxide dismutase antioxidant (SOD) are verified identifiers for the efficiency of VO(IV)/FA/AA n system compounds as antidiabetic drug agents., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Pyrazolo[1,5- a ]pyrimidines 5a - c , 9a - c and 13a - i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5- a ]pyrimidines showed that the pyrazolo[1,5- a ]pyrimidines ( 5c , 9a , 9c , 13a , 13c , 13d , 13e and 13h ) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5- a ]pyrimidines 5a - c , 9a - c and 13a - i confirmed that most of the compounds (i) were within the range set by Lipinski's rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c , 9a , 9c , 13a , 13c , 13d , 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.

As important cancer therapeutic agents, macrocyclic peptides have recently drawn great attention, mainly because they are synthetically accessible and have lower toxicity towards normal cells. In the present work, we synthesized newly macrocyclic pyridoheptapeptide derivatives. The synthesized derivatives were characterized using standard chemical and spectroscopic analytical techniques, and their anticancer activities against human breast and hepatocellular cancer cells were investigated. Results showed that compounds 1a and 1b were the most effective against hepatocellular (HepG2) and breast (MCF-7) cancer cell lines, respectively.

A series of branched tetrapeptide Schiff bases 3 - 6 were designed and synthesized from corresponding tetrapeptide hydrazide 2 as a starting material.In vitroevaluation of the synthesized compounds 4 - 6 against breast MCF-7 carcinoma cells identified their excellent anticancer potency, with IC 50 ranging from 8.12 ± 0.14 to 17.55 ± 0.27 μM in comparison with the references, cisplatin and milaplatin (IC 50 = 13.34 ± 0.11and 18.43 ± 0.13 μM, respectively). Furthermore, all derivatives demonstrated promising activity upon evaluation of theirin vitroandin vivosuppression of p53 ubiquitination and inhibition assessment for LDHA kinase. Finally, molecular docking studies were performed to predict the possible binding features of the potent derivatives within the ATP pocket of LDHA in an attempt to get a lead for developing a more potent LDHA inhibitor with anti-proliferative potency.

The current study was chiefly designed to examine the antiproliferative and antioxidant activities of some novel quinazolinone(thione) derivatives 6 - 14 . The present work focused on two main points; firstly, comparing between quinazolinone and quinazolinthione derivatives. Whereas, antiproliferative (against two cell lines namely, HepG2 and MCF-7) and antioxidant (by two methods; ABTS and DPPH) activities of the investigated compounds, the best quinazolinthione derivatives were 6 and 14, which exhibited excellent potencies comparable to quinazolinone derivatives 5 and 9 , respectively. Secondly, we compared the activity of four series of Schiff bases which included the quinazolinone moiety ( 11a - d ). In addition, the antiproliferative and antioxidant activities of the compounds with various aryl aldehyde hydrazone derivatives ( 11a - d ) analogs were studied. The compounds exhibited potency that increased with increasing electron donating group in p -position (OH > OMe > Cl) due to extended conjugated systems. Noteworthy, most of antiproliferative and antioxidant activities results for the tested compounds are consistent with the DFT calculations.

A series of Schiff bases 14 - 25 were designed and synthesized for evaluation of their antibacterial properties against multi-drug resistant bacteria (MDRB). The antibacterial activities of Schiff bases 14 - 25 showed that most of the synthesized compounds displayed a significant antibacterial activity. Assessment of in silico ADMET properties (absorption, distribution, metabolism, excretion and toxicity) of Schiff bases illustrates that all derivatives showed agreement to the Lipinski's rule of five. Further enzymatic assay aided by molecular docking study demonstrated that compound 18 is a potent inhibitor of staphylococcus aureus DNA gyrase and dihydrofolate reductase kinases. This study could be valuable in the discovery of new potent antimicrobial agents.

A series of 4-(1 H -1,2,4-triazol-1-yl)benzoic acid hybrids (1-17) was successfully synthesized and their structures were established by NMR and MS analysis. In vitro cytotoxic evaluation indicated that some of the hybrids exhibited potent inhibitory activities against MCF-7 and HCT-116 cancer cell lines, with IC 50 values ranging from 15.6 to 23.9 µM, compared with reference drug doxorubicin (19.7 and 22.6 µM, respectively). Notably, the most potent compounds, 2, 5, 14, and 15, not only exhibited an obvious improvement in IC 50 values, but demonstrated very weak cytotoxic effects toward normal cells (RPE-1) compared with doxorubicin. A further investigation showed that compounds 2 and 14 clearly inhibited the proliferation of MCF-7 cancer cells by inducing apoptosis. In addition, these hybrids showed acceptable correlation with bioassay results in regression plots generated by 2D QSAR models. Our results indicated that 1,2,4-triazole benzoic acid hybrids could be used as a structural optimization platform for the design and development of more selective and potent anticancer molecules., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Aim: This research paper is aimed at designing a novel insulin alternative for the treatment of diabetes. Materials & methods: Six novel vanadyl(II) compounds, [(AMP -2 )(VO +2 )(AA n -1 )]·NH 4 +1 , were synthesized from an equimolar ratio of adenosine monophosphate, VOSO 4 and amino acids (AA n ). Results: The magnetic moments and electronic spectra revealed the square pyramidal geometrical structure of the complexes. In an in vivo study, the insulin levels, blood glucose levels, lipid profiles and histology of the pancreas and liver of the animals treated with the complexes were similar to those of healthy control animals, unlike the untreated and vanadyl sulfate(II)-treated diabetic ones. Conclusion: The data gathered in the current research illustrated that vanadyl(II)-AMP-amino acid (AA) mixed-ligand complexes can function as antidiabetic agents.

Diabetes is an increasingly common metabolic disorder with high comorbidity and societal and personal costs. Insulin replacement therapy is limited by a lack of oral bioavailability. Recent studies suggest vanadium has therapeutic potential. A newly synthesized complex between oxidovanadium (IV) and orotic acid (OAH 3 ), [(OAH 1 )(VO)(NH 3 ) 2 ].3H 2 O, was characterized using spectroscopic and thermogravimetric techniques. In vivo potential was assessed in a streptozocin-induced rat model of diabetes. OAH 3 acts as a bidentate ligand in the formation of the dark green, crystalline oxidovanadium (IV) complex in a square pyramidal configuration. Treatment with oxidovanadium (IV)-orotate in vivo significantly improved many biochemical parameters with minimal toxicity and restored pancreatic and hepatic histology. The results of the present work describe a safe, new compound for the treatment of diabetes.

Dihydropyrimidinone derivatives containing piperidine moiety were synthesised in a good yield. All the compounds were confirmed by elemental analysis and spectral data. Anti-ulcer activity of novel dihydropyrimidinone-piperidine hybrids (1-18) was evaluated. Among them, four compounds (3, 8, 11 and 15) were found to be most active in 80% ethanol-induced ulcer experimental animal model. All the potent compounds were further evaluated for anti-ulcer activity by different in vivo anti-ulcer models to study the effect of compounds on anti-secretory and cytoprotective activities. All the active compounds inhibited the formation of gastric ulcers and increased the formation of gastric mucin secretion. Compound 15 was found to be the most potent compound of the series as anti-ulcer agent. Additional experimental studies on lead compound 15 will result in a new class of orally active molecule for anti-ulcer activity.

Enaminones, 4-methyl-1-[4-(piperazin/morpholin-1-yl) phenyl] pent-2-en-1-one ( IIa ⁻ b ) were synthesized by refluxing 1-[4-(piperazin/morpholin-1-yl) phenyl] ethan-1-one ( Ia ⁻ b ) with dimethylformamide dimethylacetal (DMF⁻DMA) without any solvent. The three dimensional structure of enaminone ( IIb ) containing morpholine moiety was confirmed by single crystal X-ray crystallography. Finally, the dihydropyrimidinone derivatives ( 1 ⁻ 20 ) were obtained by reacting enaminones ( IIa ⁻ b ) with urea and different substituted benzaldehydes in the presence of glacial acetic acid. Dihydropyrimidinone derivatives containing piperazine/morpholine moiety were synthesized in a good yield by means of simple and efficient method.