EGFR Inhibition by Novel Thiazole Derivatives: Insights from Docking Studies and Experimental Validation

Abstract

Molecular docking studies were conducted on promising compounds to elucidate their enzymatic activities based on binding interactions with the receptor. Among the compounds investigated, PVS 03 demonstrated the highest docking score of -7.811, indicating a strong affinity towards the receptor compared to others. Notably, it formed hydrophobic bonds with C10, C17, C18, and C14, which are crucial for anticancer activity. The compounds were synthesized via traditional methods, with reaction progress monitored using the TCL method. Percent yields revealed PVS 01 with the highest yield, whereas PVS 04 exhibited lower yield (Table 4). Additionally, % purity was assessed using the HPLC method, highlighting PVS 10's greater purity compared to PVS 04 in the series of novel thiazole derivatives. These derivatives were synthesized to evaluate their in vitro anticancer activity against Hep-G2 and MDAMB-231 cell lines. PVS 03 displayed superior anticancer activity compared to dasatinib. However, PVS 06 and 07 exhibited no inhibition against MDAMB-231 cells, and PVS 05 showed no inhibition against Hep-G2 cells. In an another series, novel 2,4-disubstituted thiazole derivatives were synthesized to screen their in vitro anticancer activity against MCF-7 (Breast Cancer) and A431 (Lung Cancer cell line) cells. PVS 2.7 demonstrated the most potent anticancer activity compared to dasatinib. Nonetheless, PVS 2.10 and PVS 2.4 did not inhibit A431 cells, while PVS 2.7 did not inhibit MCF-7 cells. These results collectively suggest that the novel thiazole derivatives hold promise as EGFR inhibitors with enhanced anticancer potential.