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

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 gamma-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. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, novel fused benzothiazole-1,2,3-triazole hybrids were successfully synthesized through a CuI catalyzed method, showing promising anticancer activity against human cancer cell lines. The compounds 5i, 5n, 5o, 5 h and 5l demonstrated superior activity, supported by in vitro and in silico ADME studies as well as molecular docking studies on human gamma-tubulin receptor.