Benzothiazole-[1,2,3]triazolo[5,1-a]isoindoles: Synthesis, anticancer activity, bioavailability and in silico studies against Gama-Tubulin protein

Abstract

We, herein, reported the CuI catalyzed synthesis of some novel fused benzothiazole-1,2,3-triazole hybrids (5a-5o) in one-pot. The in vitro anticancer activity of these compounds revealed that the compounds 5 h, 5i, 5l, 5n and 5o showed superior activity against human cancer cell lines like MCF-7, A-549, DU-145 and HeLa than the standard Etoposide. Remarkably, the in vitro tubulin polymerization inhibitory assay of compounds 5 h, 5i, 5l, 5n and 5o revealed that the compounds 5i and 5l showed superior activity than the standard CA-4, while the compounds 5 h, 5n and 5o were shown comparable activity with the CA-4. Besides, the results of in vitro and in silico ADME studies of most potent compounds 5i, 5n, 5o, 5 h and 5l were supported the corresponding in vitro anticancer activity data. Finally, the molecular docking studies of compounds (5a–5o) on human γ-tubulin receptor suggested that the most potent compounds 5i, 5n, 5o, 5 h and 5l strongly bind to the protein and energy calculations were in good agreement with the corresponding IC50 values.