Imidazo[1,2‐a]Pyridine‐1,2,4‐Oxadiazoles as Potent Anticancer Agents: Study of EGFR Inhibition and Molecular Docking Studies

ABSTRACT In an effort to discover prospective anticancer medicines, a novel series of imidazo[1,2‐a]pyridine‐1,2,4‐oxadiazole hybrids was synthesized and tested for their anti‐lung cancer activity in vitro against lung cancer cell lines (A549 and NCI‐H460). The results of this study were analyzed. Both compounds (8‐(((5‐(3,5‐difluorophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)amino)‐2‐methylimidazo[1,2‐a]pyridin‐3‐yl)(morpholino)methanone and (8‐(((5‐(3,5‐dichlorophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)amino)‐2‐methylimidazo[1,2‐a]pyridin‐3‐yl) (morpholino)methanone had the greatest potency on both cancer cells, with IC 50 values of 2.35 ± 0.31 and 3.46 ± 0.26 µM against A‐549 and 5.21 ± 0.28 and 4.65 ± 0.19 µM against NCI‐H460, respectively, among the compounds that were evaluated. This comparison is made with the standard drug erlotinib, which has a concentration of 4.43 ± 0.21 µM in A‐549 and 7.56 ± 0.32 µM in NCI‐H460. According to the results of EGFR inhibitory tests, compound (8‐(((5‐(3,5‐dichlorophenyl)‐1,2,4‐oxadiazol‐3‐yl)methyl)amino)‐2‐methylimidazo[1,2‐a]pyridin‐3‐yl)(morpholino)methanone (IC 50 = 0.31 ± 0.02 µM) exhibited a higher level of effectiveness in vitro when compared to the standard erlotinib (IC 50 = 0.42 ± 0.01 µM). Additionally, in silico research of four potent compounds were carried out in order to identify their interactions with the EGFR receptor. The energy estimations obtained from these investigations were in agreement with the IC 50 values that were documented.