Drug repurposing strategy to identify the putative leads against the Epidermal growth factor receptor (EGFR) from the USFDA-approved drug pool: Investigating the utility as an anticancer agent. (PubMed, J Mol Graph Model)
The initial HTVS (high-throughput virtual screening), followed by XP analysis and molecular mechanics (MMGBSA) and ADME profiling, led to the identification of Cycloguanil (antimalarial) and Metformin (antidiabetic) as the putative lead molecules with the potential to inhibit the EGFR...Cycloguanil inhibited the EGFR with a half maximal inhibitory concentration (IC50) of IC50 of 490 nM compared to erlotinib with an IC50 of 222 nM...From the analysis, it was deduced that cycloguanil exhibited the most potent cytotoxicity towards the A549 cell with an IC50 of 6.83 μM, followed by HCT-116 with an IC50 of 9.32 μM, while in MCF-7, it exhibited an IC50 of 14.82 μM. The lead molecule, cycloguanil, may plausibly serve as an important template that may be optimized by performing bioisosteric replacements, leading to a putative kinase inhibitor with a potent anticancer profile.