Synthesis and biological evaluation of bergenin-1,2,3-triazole hybrids as novel class of anti-mitotic agents

• Published in: Bioorganic chemistry 2019-10, Vol.91, p.103161-103161, Article 103161
• Main Authors: Pavan Kumar, P., Siva, Bandi, Venkateswara Rao, Banoth, Dileep Kumar, G., Lakshma Nayak, V., Nishant Jain, S., Tiwari, Ashok K, Purushotham, U., Venkata Rao, C., Suresh Babu, K.
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazole hybrids; Bergenin; Cytotoxic activity; Mallotus philippensis
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103161

A series of bergenin-triazole hybrids were synthesized based on “Click” reaction and tested for cytotoxic activities. Among the congeners, 4j showed potent activity against HeLa cells. Further cell cycle analysis indicated that it potently arrested cell growth at G2/M phase. [Display omitted] •Bergenin-12,3-triazole hybrids were synthesized.•Among derivatives, 4j manifested potent cytotoxic activity.•Cell cycle analysis indicated 4j arrested HeLa cells at G2/M phase.•In vivo tubulin polymerization assay show that 4j disrupts tubulin assembly. In continuation of our investigation of pharmacologically-motivated natural products, we have isolated bergenin (1) as a major compound from Mallotus philippensis, which is deployed in different Indian traditional systems of medicine. Here, a series of bergenin-1,2,3-triazole hybrids were synthesized and evaluated for their potentials against a panel of cancer cell lines. Several of the hybrid derivatives were found more potent in comparison to parent compound bergenin (1). Among them, 4j demonstrated potent activity against A-549 and HeLa cell lines with IC50 values of 1.86 µM and 1.33 μM, respectively, and was equipotent to doxorubicin. Cell cycle analysis showed that 4j arrested HeLa cells at G2/M phase and lead to accumulation of Cyclin B1 protein. Cell based tubulin polymerization assays and docking studies demonstrated that 4j disrupts tubulin assembly by occupying colchicine binding pocket of tubulin.