29 results on '"Umair Ilyas"'
Search Results
2. Corrigendum: Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis
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Reem Altaf, Umair Ilyas, Anmei Ma, and Meiqi Shi
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NSCLC ,mutational analysis ,differentially expressed genes ,microarray ,bioinformatics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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3. Identification and validation of differentially expressed genes for targeted therapy in NSCLC using integrated bioinformatics analysis
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Reem Altaf, Umair Ilyas, Anmei Ma, and Meiqi Shi
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NSCLC ,mutational analysis ,differentially expressed genes ,microarray ,bioinformatics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundDespite the high prevalence of lung cancer, with a five-year survival rate of only 23%, the underlying molecular mechanisms of non-small cell lung cancer (NSCLC) remain unknown. There is a great need to identify reliable candidate biomarker genes for early diagnosis and targeted therapeutic strategies to prevent cancer progression.MethodsIn this study, four datasets obtained from the Gene Expression Omnibus were evaluated for NSCLC- associated differentially expressed genes (DEGs) using bioinformatics analysis. About 10 common significant DEGs were shortlisted based on their p-value and FDR (DOCK4, ID2, SASH1, NPR1, GJA4, TBX2, CD24, HBEGF, GATA3, and DDR1). The expression of significant genes was validated using experimental data obtained from TCGA and the Human Protein Atlas database. The human proteomic data for post- translational modifications was used to interpret the mutations in these genes.ResultsValidation of DEGs revealed a significant difference in the expression of hub genes in normal and tumor tissues. Mutation analysis revealed 22.69%, 48.95%, and 47.21% sequence predicted disordered regions of DOCK4, GJA4, and HBEGF, respectively. The gene-gene and drug-gene network analysis revealed important interactions between genes and chemicals suggesting they could act as probable drug targets. The system-level network showed important interactions between these genes, and the drug interaction network showed that these genes are affected by several types of chemicals that could serve as potential drug targets.ConclusionsThe study demonstrates the importance of systemic genetics in identifying potential drug- targeted therapies for NSCLC. The integrative system- level approach should contribute to a better understanding of disease etiology and may accelerate drug discovery for many cancer types.
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- 2023
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4. Synthesis, Biological Evaluation, 2D-QSAR, and Molecular Simulation Studies of Dihydropyrimidinone Derivatives as Alkaline Phosphatase Inhibitors
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Reem Altaf, Humaira Nadeem, Muhammad Nasir Iqbal, Umair Ilyas, Zaman Ashraf, Muhammad Imran, and Syed Aun Muhammad
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Chemistry ,QD1-999 - Published
- 2022
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5. Virtual screening and drug repositioning of FDA-approved drugs from the ZINC database to identify the potential hTERT inhibitors
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Hasan Afzaal, Reem Altaf, Umair Ilyas, Shaiq Uz Zaman, Syed Damin Abbas Hamdani, Saifullah Khan, Hajra Zafar, Mustafeez Mujtaba Babar, and Yongtao Duan
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hTERT inhibitors ,virtual screening ,drug repurposing ,molecular dynamic simulation ,anticancer ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The length of the telomeres is maintained with the help of the enzyme telomerase constituting of two components, namely, a core reverse transcriptase protein (hTERT) and RNA (hTR). It serves as a significant and universal cancer target. In silico approaches play a crucial role in accelerating drug development processes, especially cancer drug repurposing is an attractive approach. The current study is aimed at the repurposing of FDA-approved drugs for their potential role as hTERT inhibitors. Accordingly, a library of 2,915 sets of FDA-approved drugs was generated from the ZINC database in order to screen for novel hTERT inhibitors; later on, these were subjected to molecular docking analysis. The top two hits, ZINC03784182 and ZINC01530694, were shortlisted for molecular dynamic simulation studies at 100 ns based on their binding scores. The RMSD, RMSF, Rg, SASA, and interaction energies were calculated for a 100-ns simulation period. The hit compounds were also analyzed for antitumor activity, and the results revealed promising cytotoxic activities of these compounds. The study has revealed the potential application of these drugs as antitumor agents that can be useful in treating cancer and can serve as lead compounds for further in vivo, in vitro, and clinical studies.
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- 2022
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6. Investigation of anti-diabetic potential and molecular simulation studies of dihydropyrimidinone derivatives
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Umair Ilyas, Bisma Nazir, Reem Altaf, Syed Aun Muhammad, Hajra Zafar, Ana Cláudia Paiva-Santos, Muhammad Abbas, and Yongtao Duan
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Dihydropyrimidinones ,alpha-glucosidase ,molecular docking ,anti-diabetic ,in-silico ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
In an attempt to find new targets for α-amylase and α-glucosidase for the treatment of type 2 diabetes mellitus, the present study aims in determining the anti-diabetic potential of synthesized dihydropyrimidinone derivatives. The in vitro α-glucosidase and α-amylase inhibitory activity was performed and the molecular docking analysis of the ligand in the active binding site of target protein was determined. The results revealed significant percent inhibition of α-glucosidase by the compound 6-benzyl-4-(4-hydroxyphenyl)-3,4,6,7-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione (compound A). The active compound showed 81.99% inhibition when compared to standard ascorbic acid having percent inhibition 81.18%. The IC50 of active compound (A) showed to be 1.02 µg/ml. The molecular docking analysis revealed that the ligand bound to the active binding site of protein with the lowest binding energy of -7.9 kcal/mol that was also significantly similar to standard having -7.8 kcal/mol binding energy. The molecular dynamic simulation studies also revealed stable binding of ligand in the active binding site of protein with low RMSD of 1.7 Å similar to the protein RMSD 1.6Å In conclusion, the study revealed a potential new target against α-glucosidase to treat type 2 diabetes mellitus.
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- 2022
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7. Herbal therapies in gastrointestinal and hepatic disorders: An evidence-based clinical review
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Yongfang Yao, Murad Habib, Hajra Fazeelat Bajwa, Anina Qureshi, Rameesha Fareed, Reem Altaf, Umair Ilyas, Yongtao Duan, and Muhammad Abbas
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ethnopharmacology ,herbal medication ,GIT ,liver ,treatment ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The gastrointestinal tract (GIT) and the liver constitute the major organs of the human body. Indeed, the very survival of the human body depends on their proper functioning. Because the GIT is a huge and complex organ system, the maintenance of proper GIT and liver health is an arduous task. GIT disturbances such as diarrhea, stomach ache, flatulence, constipation, nausea, and vomiting are very common, and they contribute to a significant burden on the healthcare system. Pharmacies are full of over-the-counter pharmacological drugs to alleviate its common conditions. However, these drugs do not always prove to be fully effective and patients have to keep on living with these ailments without a proper and long-term solution. The aim of this review article is to present a practical reference guide to the role of herbal medicines in dealing with gastrointestinal and hepatic disorders, which is supported by systematic reviews and evidence-based trials. People have depended on herbal medications for centuries for the treatment of various ailments of the GIT, liver, and other organ system problems. Recently, this trend of incorporating herbal medication for the treatment of various diseases in both developing and developed countries have surged. Many people continue to use herbal medications, even though substantial data about their efficacy, uses, and toxicological effects do not exist. In addition, while herbal medicines have enormous benefits in both the prevention and the treatment of medical ailments, they can also have toxicological effects. It is, therefore, of the utmost importance that appropriate time, energy, and resources are spent on the development of ethnopharmacology. In addition, herbal products should be classified in a pattern similar to pharmacological medications, including their uses, side effects, mechanism of action, efficacy, and so on.
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- 2022
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8. Recent advances in immune checkpoint inhibitors for non-small lung cancer treatment
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Reem Altaf, Sarmad Sheraz Jadoon, Syed Aun Muhammad, Umair Ilyas, and Yongtao Duan
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lung cancer ,immune checkpoint inhibitors ,immunotherapy ,non-small lung cancer ,chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Lung cancer is one of the deadliest types of cancer responsible for thousands of cancer-related deaths. Its treatment has remained a challenge for researchers, but an increase in the knowledge of molecular pathways and biology of lung cancer has dramatically changed its management in recent decades. Immunotherapies and immunomodulation of lung cancer have previously failed for a long time but thanks to continuous research work and enthusiasm, now, this field is emerging as a novel effective therapy. Now, it is hope with potential benefits and promising results in the treatment of lung cancer. This review article focuses on immune checkpoints inhibitors: CTLA-4 inhibitors (ipilimumab and tremelimumab) and PDL-1 inhibitors (durvalumab and atezolizumab) that can be blocked to treat lung carcinoma. It is also focused on critically analyzing different studies and clinical trials to determine the potential benefits, risks, and adverse events associated with immunotherapeutic treatment.
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- 2022
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9. A meta-analysis of genome-wide gene expression differences identifies promising targets for type 2 diabetes mellitus
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Tao Huang, Bisma Nazir, Reem Altaf, Bolun Zang, Hajra Zafar, Ana Cláudia Paiva-Santos, Nabeela Niaz, Muhammad Imran, Yongtao Duan, Muhammad Abbas, and Umair Ilyas
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type 2 diabetes mellitus ,gene ontology ,differential expression analysis ,R programming ,system biology ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Aims/introductionDue to the heterogeneous nature of type 2 diabetes mellitus and its complex effects on hemodynamics, there is a need to identify new candidate markers which are involved in the development of type 2 diabetes mellitus (DM) and can serve as potential targets. As the global diabetes prevalence in 2019 was estimated as 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045, the need to limit this rapid prevalence is of concern. The study aims to identify the possible biomarkers of type 2 diabetes mellitus with the help of the system biology approach using R programming.Materials and methodsSeveral target proteins that were found to be associated with the source genes were further curated for their role in type 2 diabetes mellitus. The differential expression analysis provided 50 differentially expressed genes by pairwise comparison between the biologically comparable groups out of which eight differentially expressed genes were short-listed. These DEGs were as follows: MCL1, PTX3, CYP3A4, PTGS1, SSTR2, SERPINA3, TDO2, and GALNT7.ResultsThe cluster analysis showed clear differences between the control and treated groups. The functional relationship of the signature genes showed a protein–protein interaction network with the target protein. Moreover, several transcriptional factors such as DBX2, HOXB7, POU3F4, MSX2, EBF1, and E4F1 showed association with these identified differentially expressed genes.ConclusionsThe study highlighted the important markers for diabetes mellitus that have shown interaction with other proteins having a role in the progression of diabetes mellitus that can serve as new targets in the management of DM.
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- 2022
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10. Nanostructured Lipid Carrier-Based Delivery of Pioglitazone for Treatment of Type 2 Diabetes
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Umair Ilyas, Muhammad Asif, Minglian Wang, Reem Altaf, Hajra Zafar, Mirza Muhammad Faran Ashraf Baig, Ana Cláudia Paiva-Santos, and Muhammad Abbas
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pioglitazone ,poor aqueous solubility ,NLCs ,nanoparticles ,diabetes ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Pioglitazone (PGZ) is utilized as a therapeutic agent in the management of (type 2) diabetes to control blood glucose levels. The existing research work was intended to make and optimize PGZ-containing NLCs (nanostructured lipid carriers). The fabricated nanostructured lipid carrier preparation was optimized by using different concentrations of the surfactants (Tween 80 and Span 80) and solid lipid (Compritol® 888 ATO) and liquid lipid (Labrasol®) while keeping the concentration of drug (PGZ), and co-surfactants (poloxamer 188) the same. The optimized NLC formulation (PGZ-NLCs) was further assessed for physical and chemical characterization, in vitro PGZ release, and stability studies. The optimized PGZ-NLCs have shown an average diameter of 150.4 nm, EE of 92.53%, PDI value of 0.076, and zeta-potential of −29.1 mV, correspondingly. The DSC thermal analysis and XRD diffractograms had not presented the spectrum of PGZ, confirming the comprehensive encapsulation of PGZ in the lipid core. PGZ-NLCs showed significantly extended release (51% in 24 h) compared to the unformulated PGZ. Our study findings confirmed that PGZ-NLCs can be a promising drug delivery system for the treatment of type 2 diabetes.
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- 2022
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11. Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development
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Reem Altaf, Humaira Nadeem, Mustafeez Mujtaba Babar, Umair Ilyas, and Syed Aun Muhammad
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Breast cancer ,Microarray datasets ,Pathway enrichment analysis ,Gene ontology ,miRNA ,Drug-gene network ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. Methods Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. Results From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these genes in breast cancer and their interaction with other signaling pathways involved in the progression of disease metastasis. The miRNA targets identified through miRDB predictor provided potential miRNA targets for these genes that can be involved in breast cancer progression. Several FDA approved drug targets were identified for the signature genes easing the therapeutic options for breast cancer treatment. Conclusion The study provides a more clarified role of signature genes, their interaction with other genes as well as signaling pathways. The miRNA prediction and the potential drugs identified will aid in assessing the role of these targets in breast cancer.
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- 2021
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12. Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach
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Umair Ilyas, Shaiq uz Zaman, Reem Altaf, Humaira Nadeem, and Syed Aun Muhammad
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Colorectal cancer ,Microarrays ,Functional genomics ,PPI network ,Biomarkers ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value
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- 2020
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13. 1,3,4-Oxadiazole Derivative Attenuates Chronic Constriction Injury Induced Neuropathic Pain: A Computational, Behavioral, and Molecular Approach
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Muhammad Faheem, Syed Hussain Ali, Abdul Waheed Khan, Mahboob Alam, Umair Ilyas, Muhammad Zahoor, Muhammad Umar Khayam Sahibzada, Sidra Khalid, Riaz Ullah, Ali S. Alqahtani, and Abdulaziz M. Alqahtani
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In-silico ,chronic constriction injury ,hyperalgesia ,neuro-protective ,IL-6 ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The production and up-regulation of inflammatory mediators are contributing factors for the development and maintenance of neuropathic pain. In the present study, the post-treatment of synthetic 1,3,4 oxadiazole derivative (B3) for its neuroprotective potential in chronic constriction injury-induced neuropathic pain was applied. In-silico studies were carried out through Auto Dock, PyRx, and DSV to obtain the possible binding and interactions of the ligands (B3) with COX-2, IL-6, and iNOS. The sciatic nerve of the anesthetized rat was constricted with sutures 3/0. Treatment with 1,3,4-oxadiazole derivative was started a day after surgery and continued until the 14th day. All behavioral studies were executed on day 0, 3rd, 7th, 10th, and 14th. The sciatic nerve and spinal cord were collected for further molecular analysis. The interactions in the form of hydrogen bonding stabilizes the ligand target complex. B3 showed three hydrogen bonds with IL-6. B3, in addition to correcting paw posture/deformation induced by CCI, attenuates hyperalgesia (p < 0.001) and allodynia (p < 0.001). B3 significantly raised the level of GST and GSH in both the sciatic nerve and spinal cord and reduced the LPO and iNOS (p < 0.001). B3 attenuates the pathological changes induced by nerve injury, which was confirmed by H&E staining and IHC examination. B3 down-regulates the over-expression of the inflammatory mediator IL-6 and hence provides neuroprotective effects in CCI-induced pain. The results demonstrate that B3 possess anti-nociceptive and anti-hyperalgesic effects and thus minimizes pain perception and inflammation. The possible underlying mechanism for the neuroprotective effect of B3 probably may be mediated through IL-6.
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- 2020
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14. Correction to: Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach
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Umair Ilyas, Shahiq uz Zaman, Reem Altaf, Humaira Nadeem, and Syed Aun Muhammad
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Biology (General) ,QH301-705.5 - Abstract
An amendment to this paper has been published and can be accessed via the original article.
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- 2020
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15. Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives as Potential Anticancer Agents
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Umair, Ilyas, Lina Tariq, Alkury, Shagufta, Naaz, Syed Aun, Muhammad, Humaira, Nadeem, Reem, Altaf, Shahiq Uz, Zaman, Muhammad, Faheem, Imran, Sajid, Mohsin Tasawar, Cheema, Abdul, Mannan, Fawad Ali, Shah, and Shupeng, Li
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Pharmacology ,Cancer Research ,Molecular Structure ,Aminopyridines ,Antineoplastic Agents ,Molecular Docking Simulation ,Structure-Activity Relationship ,Cell Line, Tumor ,Humans ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Colorectal Neoplasms ,beta Catenin ,Cell Proliferation - Abstract
Background: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure. Objectives: The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2- aminopyridine could attenuate tumor development using colorectal cancer cell lines. Methods: Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay. Results: Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay. Conclusion: In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.
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- 2022
16. Ceftriaxone Injectables: An In vitro Evaluation of Antimicrobial Activity and Comparative Efficacy
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Umair Ilyas, Reem Altaf, Sumayya Zaheer, and Muhammad Ijaz-Ul-Haq
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Aims: The objective of the current study was to compare the In Vitro efficacy of regionally produced brands of ceftriaxone with that of the global innovator brand. Therefore, a fact-based conclusion at the end of the study will serve to dispel any uncertainty regarding the efficacy of medications produced locally, whether they are inferior or equal in their comparative activity. Study Design: This study was In Vitro Lab based study. Place and Duration of Study: The study was performed in Riphah International University, Department of Pharmacy from July 2021 to August 2021. Methodology: Five regional brands and one international parent brand (Rocephin) were chosen. The multinational product was regarded as the standard. Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aurogenosa were the four bacterial strains against which activities were tested. Antibiotics' zone of inhibition was measured using the agar well method, and their minimum inhibitory concentration was identified using the broth dilution method. Results: All tested brands showed effectiveness against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aurogenosa.Some of the brands at some point showed more In Vitro efficacy than the standard brand. Conclusion: Health care professionals can be confident in prescribing locally manufactured brands that have equivalent efficacy to their international counterparts based on the findings of the study. Healthcare professionals can suggest the generic brand in population where medicine cost is directly affecting the patients adherence to therapeutic regimen.
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- 2022
17. Investigation of 1, 3, 4 Oxadiazole Derivative in PTZ-Induced Neurodegeneration: A Simulation and Molecular Approach
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Aman Ullah, Yusuf S. Althobaiti, Abdul Waheed Khan, Syed Hussain Ali, Muhammad Faheem, and Umair Ilyas
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biology ,GABAA receptor ,Chemistry ,medicine.medical_treatment ,Immunology ,Glutathione reductase ,Glutathione ,Pharmacology ,molecular dynamic simulations ,Nitric oxide synthase ,Lipid peroxidation ,chemistry.chemical_compound ,Anticonvulsant ,gamma amino butyric acid A ,Flumazenil ,docking ,medicine ,biology.protein ,Immunology and Allergy ,Journal of Inflammation Research ,Diazepam ,Original Research ,medicine.drug - Abstract
Muhammad Faheem,1 Yusuf S Althobaiti,2,3 Abdul Waheed Khan,4 Aman Ullah,1 Syed Hussain Ali,1 Umair Ilyas1 1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 2Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia; 3Addiction and Neuroscience Research Unit, Taif University, Taif, 21944, Saudi Arabia; 4Department of Pharmacy, The University of Lahore, Islamabad, PakistanCorrespondence: Muhammad Faheem; Yusuf S Althobaiti Email muhammad.faheem@riphah.edu.pk; althobaiti@tu.edu.saObjective: The study investigated the effect 5-[(naphthalen-2-yloxy) methyl]-1,3,4-oxadiaszole2-thiol (B3) in animal model of acute epileptic shock.Methods: The pharmacokinetics profile of B3 was checked through SwissADME software. The binding affinities of B3, diazepam, and flumazenil (FLZ) were obtained through Auto Dock and PyRx. Post docking analysis and interpretation of hydrogen bonds were performed through Discovery Studio Visualizer 2016. Molecular dynamics simulations of three complexes were carried out through Desmond software package. B3 was then proceeded in PTZ-induced acute seizures models. Flumazenil was used in animal studies for elucidation of possible mechanism of B3. After behavioral studies, the animals were sacrificed, and the brain samples were isolated and stored in 4% formalin for molecular investigations including H and E staining, IHC staining and Elisa etc.Results: The results demonstrate that B3 at 20 and 40 mg/kg prolonged the onset time of generalized seizures. B3 considerably increased the expression of protective glutathione S-transferase and glutathione reductase and reduced lipid peroxidation and inducible nitric oxide synthase (P < 0.001) in the cortex. B3 significantly suppressed (P < 0.01) the over expression of the inflammatory mediator tumor necrosis factorâα, whose up-regulation is reported in acute epileptic shocks.Conclusion: Hence, it is concluded from the aforementioned results that B3 provides neuroprotective effects PTZ-induced acute epileptic model. FLZ pretreatment resulted in inhibition of the anticonvulsant effect of B3. B3 possesses anticonvulsant effect which may be mediated through GABAA mediated antiepileptic pathway.Keywords: docking, molecular dynamic simulations, gamma amino butyric acid A
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- 2021
18. LOGISTIC DEVELOPMENT STRATEGY FOR PHARMACEUTICAL INDUSTRY FOLLOWING LEAN PERSPECTIVE: THE CASE STUDY OF PAKISTAN
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Muhammad Umair Ilyas, Dr. Shameel Ahmed Zuberi, Dr. Muhammad Kashif
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Pharmaceutical strategies are typically unseen to patients but have a direct impact on how well healthcare is managed. This study focuses on creating a new strategy to further develop the coordinated elements supporting the pharmaceutical divisions. The study focuses on the administration and network of stores for pharmaceutical materials used in this sector in Pakistan. This study investigates previous studies to develop an improvement strategy to computerise the systems used in the distribution center and outbuildings. The study explores the impact of the disagreements between pharmaceutical organizations on the business and their commitment to the development of strategies along with recognizing the best-known strategies of pharmaceutical development and their benefits. It also offers best practices and develops a structure of understanding with respect to the pharmaceutical companies in Pakistan. The study finds that the pharmaceuticaldevelopment and its situation in Pakistan is exceptionally unique and rapidly evolving. The study formulates new strategic proposals within the broader political context of Pakistan and its pharmaceutical industry.
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- 2022
19. LOGISTIC DEVELOPMENT STRATEGY FOR PHARMACEUTICAL INDUSTRY FOLLOWING LEAN PERSPECTIVE: THE CASE STUDY OF PAKISTAN
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Dr. Shameel Ahmed Zuberi, Dr. Muhammad Kashif, Muhammad Umair Ilyas,, primary
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- 2022
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20. Insilico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors.
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Syed Aun Muhammad, Amjad Ali 0001, Tariq Ismail, Rehan Zafar Paracha, Umair Ilyas, and Jamil Ahmad
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- 2014
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21. Genomic and Epigenomic Features of Glioblastoma Multiforme and its Biomarkers
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Sarmad Sheraz Jadoon, Umair Ilyas, Hajra Zafar, Ana Cláudia Paiva-Santos, Saifullah Khan, Saeed Ahmad Khan, Tanzeel Ahmed, Yasir Rasool, Reem Altaf, Faisal Raza, and Muhammad Abbas
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Oncology - Abstract
Glioblastoma multiforme is a serious and life-threatening tumor of central nervous system, characterized by aggressive behavior, poor prognosis, and low survival rate. Despite of the availability of aggressive antitumor therapeutic regimen for glioblastoma (radiotherapy followed by chemotherapeutic dose), recovery rate, and patients’ survival ratio is attributed to the lack of selectivity of therapeutic drugs and less advancement in cancer therapeutics over last decade. Moreover, tools employed in conventional diagnosis of glioblastoma are more invasive and painful, making the process excruciating for the patients. These challenges urge for the need of novel biomarkers for diagnosis, prognosis, and prediction purpose with less invasiveness and more patient compliance. This article will explore the genetic biomarkers isocitrate dehydrogenase mutation, MGMT mutations, and EGFR that can be deployed as an analytical tool in diagnosis of disease and prognosis of a therapeutic course. The review also highlights the importance of employing novel microRNAs as prognostic biomarkers. Recent clinical advancements to treat GBM and to prevent relapse of the disease are also discussed in this article in the hope of finding a robust and effective method to treat GBM.
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- 2022
22. Cytotoxic Evaluation, Molecular Docking, and 2D-QSAR Studies of Dihydropyrimidinone Derivatives as Potential Anticancer Agents
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Reem Altaf, Humaira Nadeem, Umair Ilyas, Jamshed Iqbal, Rehan Zafar Paracha, Hajra Zafar, Ana Cláudia Paiva-Santos, Muhammad Sulaiman, and Faisal Raza
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Article Subject ,Oncology - Abstract
The diverse pharmacological role of dihydropyrimidinone scaffold has made it to be an interesting drug target. Because of the high incidence and mortality rate of breast cancer, there is a dire need of discovering new pharmacotherapeutic agents in managing this disease. A series of twenty-two derivatives of 6-(chloromethyl)-4-(4-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3a-3k) and ethyl 6-(chloromethyl)-4-(2-hydroxyphenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a-4k) synthesized in a previous study were evaluated for their anticancer potential against breast cancer cell line. Molecular docking studies were performed to analyze the binding mode and interaction pattern of these compounds against nine breast cancer target proteins. The in vitro cell proliferation assay was performed against the breast cancer cell line MCF-7. The structure activity relationship of these compounds was further studied using QSARINS. Among nine proteins, the docking analysis revealed efficient binding of compounds 4f, 4e, 3e, 4g, and 4h against all target proteins. The in vitro cytotoxic assay revealed significant anticancer activity of compound 4f having I C 50 of 2.15 μM. The compounds 4e, 3e, 4g, and 4h also showed anticancer activities with I C 50 of 2.401, 2.41, 2.47 and 2.33 μM, respectively. The standard tamoxifen showed I C 50 1.88 μM. The 2D qualitative structure-activity relationship (QSAR) analysis was also carried out to identify potential breast cancer targets through QSARINS. The final QSAR equation revealed good predictivity and statistical validation R 2 and Q 2 values for the model obtained from QSARINS was 0.98 and 0.97, respectively. The active compounds showed very good anticancer activities, and the binding analysis has revealed stable hydrogen bonding of these compounds with the target proteins. Moreover, the QSAR analysis has predicted useful information on the structural requirement of these compounds as anticancer agents with the importance of topological and autocorrelated descriptors in effecting the cancer activities.
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- 2022
23. Design, synthesis and biological evaluations of 2-aminothiazole scaffold containing amino acid moieties as anti-cancer agents
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Umair, Ilyas, Shagufta, Naz, Shahiq, Uz Zaman, Reem, Altaf, Humaira, Nadeem, Syed, Aun Muhammad, Muhammad, Faheem, and Muhammad Imran, Qadir
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Models, Molecular ,Molecular Docking Simulation ,Thiazoles ,Molecular Structure ,Protein Conformation ,Drug Design ,Animals ,Humans ,Antineoplastic Agents ,Amino Acids ,Artemia ,Colorectal Neoplasms ,HCT116 Cells - Abstract
Due to the emerging mortality rate of colorectal cancer there is a high need for the management and control of this disease. Although several treatment approaches are being developed day by day yet the high incidence rate of colorectal cancer is still not controlled. To ease in the development of treatment therapies for colorectal cancer two derivatives of ethyl 2-aminothiazole 4-carboxylate were designed and synthesized. The compounds Ethyl 2-(2-(1,3-dioxoisoindolin-2-yl)acetamido)thiazole-4-carboxylate (5a) and ethyl 2-(2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropanamido)thiazole-4-carboxylate (5b) were characterized and studied for their anti-cancer activities. The in silico molecular modeling studies were performed against the target protein beta-catenin which is an important player in the progression of colorectal cancer. The in silico ADMET studies were performed to assess the basic physicochemical properties of these compounds. The in vitro antiproliferative assay and the enzyme inhibitory assay was performed to validate the role of these compounds in the colorectal cancer. The preliminary cytotoxic assay and the MTT assay of the compounds 5a and 5b against the colorectal cancer cell line HCT 116 showed 60% inhibition of cell proliferation with IC50 of 0.72μM and 1.55μM, respectively. The standard methotrexate showed IC50 of 0.7μM showing potent inhibitory action of these compounds. The in vitro validation of the anti-cancer effect of both compounds revealed significant inhibition of beta-catenin concentration at higher doses as compared to control. Both the in vitro and in vivo assays of compounds showed effective anti-cancer activities and depicts the future potential of these compounds in colorectal cancer.
- Published
- 2021
24. Genome-scale meta-analysis of breast cancer datasets identifies promising targets for drug development
- Author
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Syed Aun Muhammad, Humaira Nadeem, Reem Altaf, Mustafeez Mujtaba Babar, and Umair Ilyas
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Microarray datasets ,Disease ,Computational biology ,Biology ,Approved drug ,Metastasis ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,microRNA ,medicine ,skin and connective tissue diseases ,lcsh:QH301-705.5 ,Gene ,miRNA ,030304 developmental biology ,0303 health sciences ,Research ,Pathway enrichment analysis ,General Medicine ,medicine.disease ,Metastatic breast cancer ,lcsh:Biology (General) ,Drug development ,030220 oncology & carcinogenesis ,Gene ontology ,Drug-gene network - Abstract
Background Because of the highly heterogeneous nature of breast cancer, each subtype differs in response to several treatment regimens. This has limited the therapeutic options for metastatic breast cancer disease requiring exploration of diverse therapeutic models to target tumor specific biomarkers. Methods Differentially expressed breast cancer genes identified through extensive data mapping were studied for their interaction with other target proteins involved in breast cancer progression. The molecular mechanisms by which these signature genes are involved in breast cancer metastasis were also studied through pathway analysis. The potential drug targets for these genes were also identified. Results From 50 DEGs, 20 genes were identified based on fold change and p-value and the data curation of these genes helped in shortlisting 8 potential gene signatures that can be used as potential candidates for breast cancer. Their network and pathway analysis clarified the role of these genes in breast cancer and their interaction with other signaling pathways involved in the progression of disease metastasis. The miRNA targets identified through miRDB predictor provided potential miRNA targets for these genes that can be involved in breast cancer progression. Several FDA approved drug targets were identified for the signature genes easing the therapeutic options for breast cancer treatment. Conclusion The study provides a more clarified role of signature genes, their interaction with other genes as well as signaling pathways. The miRNA prediction and the potential drugs identified will aid in assessing the role of these targets in breast cancer.
- Published
- 2021
25. Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach
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Shahiq uz Zaman, Umair Ilyas, Reem Altaf, Humaira Nadeem, and Syed Aun Muhammad
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PPI network ,Microarrays ,Colorectal cancer ,Systems biology ,Computational biology ,Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,lcsh:QH301-705.5 ,Gene ,030304 developmental biology ,0303 health sciences ,Research ,Wnt signaling pathway ,Correction ,Cancer ,Functional genomics ,medicine.disease ,Gene expression profiling ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,DNA microarray ,Biomarkers - Abstract
Background Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value Conclusion The integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.
- Published
- 2020
26. ADME/T Prediction, Molecular Docking, and Biological Screening of 1,2,4-Triazoles as Potential Antifungal Agents
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Umair Ilyas, Syed Aun Muhammad, Hasan Afzaal, Shahiq uz Zaman, Usman Rasheed, and Reem Altaf
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biology ,Drug discovery ,Chemistry ,Lanosterol ,Protein Data Bank (RCSB PDB) ,biology.organism_classification ,Combinatorial chemistry ,Acute toxicity ,chemistry.chemical_compound ,Docking (molecular) ,medicine ,Candida albicans ,Fluconazole ,ADME ,medicine.drug - Abstract
Clinical needs for new antifungal agents have gradually and steadily increased with the rise of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections.Triazoles are taken as potential antifungal molecules considering the existing portfolio of antifungal agents available in the market. This study was aimed to evaluate antifungal potential of 4-Amino 5-(2-Hydroxyphenyl)-1,2,4-Triazole-3-Thione and4-(2-hydroxybenzalidine)amine-5-(2-hydroxy)phenyl-1,2,4-triazole-3-thiol using molecular docking and in-vitro antifungal screening approach. This study was further designed to evaluate potential drug likeness properties and ADME/T prediction of aforementioned experimental triazoles. 3D crystal model of cytochrome P450 lanosterol 14 α-demethylaseenzyme was acquired from Protein Data Bank (PDB ID 5EQB). Docking studies revealed that both experimental compounds showed stable binding complex with lowest binding affinity values compared to reference standard Fluconazole (-6.8, -7.8 and -7.1Kcal/mol respectively for UI, UIA and Fluconazole) against cytochrome P450 lanosterol 14 α-demethylase, which is a key yeast target.In-vitro evaluation revealed that both experimental triazoles especially UIA showed promising MIC values, 24, 48 and 80 μg against Candida albican, Candida tropicalis and Candida glabrata respectively. Rat acute toxicity prediction using GUSAR model suggested that both experimental molecules were virtually non toxic when computationally studied through IV, IP, SC and oral routes of administration. This experimental work concludes that both triazoles possess strong fungicidal potential and should be further explored. In-silico work in current study further proposes an exceptional strategy for drug discovery with minimum cost and time
- Published
- 2018
27. Report: Computational drug designing of newly synthesized triazoles against potential targets of methicillin resistant Staphylococcus aureus
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Umair, Ilyas, Reem, Altaf, Syed Aun, Muhammad, Muhammad Imran, Qadir, Humaira, Nadeem, and Safia, Ahmed
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Methicillin-Resistant Staphylococcus aureus ,Magnetic Resonance Spectroscopy ,Phosphotransferases (Phosphate Group Acceptor) ,Molecular Structure ,Triazoles ,Anti-Bacterial Agents ,Molecular Docking Simulation ,Structure-Activity Relationship ,Bacterial Proteins ,Drug Design ,Spectroscopy, Fourier Transform Infrared ,Computer-Aided Design ,Molecular Targeted Therapy ,Enzyme Inhibitors ,Acyltransferases - Abstract
Methicillin resistant Staphylococcus aureus (MRSA) is resistant to known antibiotics and has become a great challenge for healthcare professionals, therefore new molecules are needed to manage this situation. In this study, new lead molecules 4-Amino-5-(2-Hydroxyphenyl)-1,2,4-Triazol-3-Thione (U1) and4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol(U1A Schiff base) were synthesized by fusion method that showed promising antibacterial activity (U1A: 26mm and U1: 14mm) against MRSA.FT-IR and NMR were used for structural characterization of these derivatives and their toxicity properties were assessed by Lipinski's rule of 5. New potential drug targets of this bacterium were also identified by comparative and subtraction genomics techniques. In particular, octanoyl-[GcvH]: protein N-octanoyl transferase and phosphor mevalonate kinase were used as potential targets in AutoDock Vina studies. This study can provide a framework to find potential drug targets for other pathogenic microorganisms that can successfully be docked with compound U1 and U1A.
- Published
- 2017
28. Assessment of the risk factors of hypertension among adultelderly group in twin cities of Pakistan
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Saba, Ishtiaq, Umair, Ilyas, Shagufta, Naz, Reem, Altaf, Hasan, Afzaal, Syed Aun, Muhammad, Shahiq, Uz Zaman, Muhammad, Imran, Fawad, Ali, Farhan, Sohail, and Sohail, Muhammad
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Adult ,Male ,Adolescent ,Urban Population ,Blood Pressure ,Middle Aged ,Young Adult ,Cross-Sectional Studies ,Risk Factors ,Hypertension ,Prevalence ,Humans ,Female ,Pakistan - Abstract
To estimate the prevalence of hypertension and to explore the risk factors associated with it.In a cross-sectional study, a population based survey was conducted on inhabitants of Rawalpindi-Islamabad region, 219 individuals; aged 18 years or above were included in the study. Blood pressure was measured along with information about individual's demographic and socio-economic characteristics were obtained using a standard questionnaire..Overall prevalence of hypertension was 29.22% (males: 21.9% and females: 78.1%) in individuals residing in Rawalpindi-Islamabad. High blood pressure is more associated with obesity (59.4%) and a progressive increase in hypertension was observed with increasing age. Bivariate analysis revealed that hypertension has a significant correlation (p-value0.05) with age, gender, family status, weight and physical health.The study concludes that our generation is well aware about the risks and consequences of hypertension, but they still continue to make no or little effort in managing or preventing it. The factors contributing to hypertension are low physical activity, diet and lack of interest to maintain their health.
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- 2017
29. In silico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors
- Author
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Amjad Ali, Jamil Ahmad, Tariq Ismail, Syed Aun Muhammad, Umair Ilyas, and Rehan Zafar
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Stereochemistry ,In silico ,Lysyl oxidase ,Antineoplastic Agents ,Plasma protein binding ,Biochemistry ,Structural Biology ,Humans ,Binding site ,Enzyme Inhibitors ,Virtual screening ,Binding Sites ,LOXL2 ,Chemistry ,Organic Chemistry ,Triazoles ,Molecular Docking Simulation ,Computational Mathematics ,Lysyl Oxidase Homolog 2 ,Tumor progression ,Drug Design ,Thermodynamics ,Amino Acid Oxidoreductases ,Hydrophobic and Hydrophilic Interactions ,Protein Binding - Abstract
Lysyl oxidase homolog 2 (LOXL2), also known as lysyl oxidase-like protein 2 is recently been explored as regulator of carcinogenesis and has been shown to be involved in tumor progression and metastasis of several carcinomas. Therefore LOXL2 has been considered as potential therapeutic target. Doing so, its inhibitors as new chemotherapeutic lead molecules: 4-amino-5-(2-hydroxyphenyl)-1,2,4-triazol-3-thione (2a) and 4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol (2b) are synthesized by fusion method (refluxed at 160 °C). Spectral analysis of these triazole derivatives are characterized by FTIR and NMR. Active binding sites and quality of the LOXL2 model is assessed by Ramachandran plots and finally drug-target analysis is performed by computational virtual screening tools. Compounds 2a and 2b showed optimum target binding affinity with -6.2 kcal/mol and -8.9 kcal/mol binding energies. This insilico study will add to our understanding of the drug designing and development, and to target cancer-causing proteins more precisely and quickly than before.
- Published
- 2014
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