Design, synthesis, anticancer evaluation and molecular docking studies of 1,2,4-oxadiazole incorporated indazole-isoxazole derivatives

Abstract

A new series of 1,2,4-oxadiazole incorporated indazole-isoxazole (12a–j) derivatives were designed, synthesized and confirmed their structures by ¹HNMR, ¹³CNMR and mass spectral analysis. Further, all compounds were evaluated for their anticancer activity against a panel of human cell lines like breast cancer (MCF-7), lung cancer (A549), prostate cancer (DU-145) and breast cancer (MDA MB-231) by using MTT assay. The etoposide used as a reference drug and the results were expressed with IC₅₀ (µM). Most of the compounds were showed good to moderate activity with respective cell lines. Among them, compounds 12b, 12e, 12 g, 12h and 12i have exhibited more potent activity as compared with the reference drug etoposide. In which one of the compound 12i has showed most significant activity. Molecular docking studies were carried out using PyRx tool and visualized through Chimera and Pymol visualization tools, revealed that the interactions between the active site of the tubulin with the selected compound 12i exhibited good interactions with the active site amino acids. These findings suggested that the 12i compound acts as a potential binder to the tubulin complex. These results revealed that the selected synthesized compounds were used in anticancer therapies.