DSpace Repository

Pharmacophore-Based Virtual Screening Approaches To Identify Novel Molecular Candidates Against EGFR Through Comprehensive Computational Approaches and In-Vitro Studies

Show simple item record

dc.contributor.author Opo, F A Dain Md
dc.contributor.author Moulay, Mohammed
dc.contributor.author Zari, Ali
dc.contributor.author Alqaderi, Afnan
dc.contributor.author Alkarim, Saleh
dc.contributor.author Zari, Talal
dc.contributor.author Bhuiyan, Mohiuddin Ahmed
dc.contributor.author Mahmoud, Maged Mostafa
dc.contributor.author Aljoud, Fadwa
dc.contributor.author Suhail, Mohd
dc.contributor.author Edris, Sherif
dc.contributor.author Ramadan, Wafaa S.
dc.contributor.author Kamal, Mohammad Amjad
dc.contributor.author Nemmiche, Saïd
dc.contributor.author Ahammad, Foysal
dc.date.accessioned 2023-06-07T05:09:21Z
dc.date.available 2023-06-07T05:09:21Z
dc.date.issued 22-11-15
dc.identifier.uri http://dspace.daffodilvarsity.edu.bd:8080/handle/123456789/10667
dc.description.abstract Alterations to the EGFR (epidermal growth factor receptor) gene, which primarily occur in the axon 18-21 position, have been linked to a variety of cancers, including ovarian, breast, colon, and lung cancer. The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. These drugs are becoming less effective in EGFR targeted cancer treatment and developing resistance to cancer cell eradication, which sometimes necessitates stopping treatment due to the side effects. One in silico study has been conducted to identify EGFR antagonists using other compounds, databases without providing the toxicity profile, comparative analyses, or morphological cell death pattern. The goal of our study was to identify potential lead compounds, and we identified seven compounds based on the docking score and four compounds that were chosen for our study, utilizing toxicity analysis. Molecular docking, virtual screening, dynamic simulation, and in-vitro screening indicated that these compounds' effects were superior to those of already marketed medication (gefitinib). The four compounds obtained, ZINC96937394, ZINC14611940, ZINC103239230, and ZINC96933670, demonstrated improved binding affinity (-9.9 kcal/mol, -9.6 kcal/mol, -9.5 kcal/mol, and -9.2 kcal/mol, respectively), interaction stability, and a lower toxicity profile. In silico toxicity analysis showed that our compounds have a lower toxicity profile and a higher LD50 value. At the same time, a selected compound, i.e., ZINC103239230, was revealed to attach to a particular active site and bind more tightly to the protein, as well as show better in-vitro results when compared to our selected gefitinib medication. MTT assay, gene expression analysis (BAX, BCL-2, and β-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC50 value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549. Keywords: EGFR; cell toxicity; gefitinib; in-vitro; inhibitors; side effects. en_US
dc.language.iso en_US en_US
dc.publisher Scopus en_US
dc.subject Lead Compounds en_US
dc.subject Treatment en_US
dc.subject Treatment process en_US
dc.title Pharmacophore-Based Virtual Screening Approaches To Identify Novel Molecular Candidates Against EGFR Through Comprehensive Computational Approaches and In-Vitro Studies en_US
dc.type Article en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Browse

My Account

Statistics