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

• Published in: Journal of molecular structure 2022-02, Vol.1250, p.131722, Article 131722
• Main Authors: Kumar N, Manoj, Nukala, Satheesh Kumar, Swamy T, Narasimha, M, Ravinder, Krishna, Thupurani Murali, Narsimha, Sirassu
• Format: Article
• Language: English
• Subjects: ADME studies; Anticancer activity; Benzothiazole-1,2,3-triazoles; Bioavailability; Human γ-tubulin; Molecular docking
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131722

•One-pot method to synthesize some novel benzothiazole-[1,2,3]triazolo[5,1-a]isoindoles.•The compounds exhibited in vitro promising anticancer activity against MCF-7, A-549, DU-145 and hela cell liness.•The results of in vitro tubulin polymerization inhibitory assay most potent compounds 5 h, 5i, 5l, 5n and 5o were also consistent with the corresponding anticancer activity data.•Transport characteristics of 5 h, 5i, 5l, 5n and 5o through Caco-2 cells have been investigated.•In silico ADME studies of compounds 5 h, 5i, 5l, 5n and 5o and in silico studies of all the compounds were also done to understand the corresponding anticancer activity. 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. [Display omitted] .