Synthesis of 1,2,3‐Triazole and Isoxazole Derivatives of [1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazine as Potent EGFR Targeting Antilung Cancer Agents

ABSTRACT Imidazole‐1,2,4triazolo[3,4‐b][1,3,4]thiadiazines associated 1,2,3‐triazole and isoxazole hybrids were designed and synthesized using a pharmacophore‐hybridization approach that incorporates physiologically active scaffolds. In vitro anticancer activity of the synthesized compounds was screened against two lung cancer cell lines, A‐549 and NCI‐H460, and results revealed that compounds 6d and 6h had substantial efficacy compared to the standard erlotinib. Furthermore, compound 6h (IC 50 = 0.61 ± 0.12 µM) exhibited greater effectiveness as compared to the conventional Erlotinib (IC 50 = 0.64 ± 0.23 µM) in vitro, as shown by EGFR inhibitory tests, whereas compound 6d (IC 50 = 0.65 ± 0.09 µM) indicated notable EGFR inhibitory action. To confirm the activity findings, five potent compounds underwent in silico molecular docking studies, with all compounds demonstrating superior binding energies relative to the standard.