Imidazo[1,2‐a]Pyrazine Linked Benzimidazole, Tetrahydropyrimidine, and 1,3,4‐Oxadizoles as Anticancer Agents

ABSTRACT Diverse libraries of Imidazo[1,2‐a]pyrazine‐Benzimidazoles, Imidazo[1,2‐a]pyrazine‐tetrahydropyrimidine, and Imidazo[1,2‐a]pyrazine‐1,3,4‐Oxadiazoles were synthesized via simple and practical cyclocondensation protocols. Structures of target compounds were established by 1 H and 13 C NMR and mass spectral analysis. These newly synthesized compounds were tested for their in vitro anticancer activity against human breast cancer (MCF‐7), lung cancer (A‐549), and liver cancer (HepG2) cell lines using Cisplatin as the standard reference. The phenyl‐substituted benzimidazole derivative 9d displayed outstanding activity against all three cell lines, with IC 50 values of 4.95 ± 0.5 μM (MCF‐7), 9.21 ± 0.7 μM (A‐549), and 10.02 ± 1.2 μM (HepG2), outperforming cisplatin (5.68 ± 0.3, 13.64 ± 0.8, and 11.82 ± 1.2 μM, respectively). Compound 9d was further evaluated through molecular docking against the crystal structure of EGFR, which had shown promising binding energy and protein‐ligand interactions. Furthermore, compound 9a demonstrated promising activity with IC 50 value of 13.38 ± 1.1 μM against HepG2 cells. The methyl carboxylate pyrimidine derivative 9f and the propyl‐substituted oxadiazole derivative 10c exhibited the strongest activities, with IC 50 values of 13.36 ± 1.1 and 10.35 ± 0.8 μM, respectively. The isopropyl substituted derivative 10d displayed good activity against MCF‐7 and HepG2 cells with an IC 50 value of 8.92 ± 0.4 and 12.45 ± 1.2 μM, respectively.