Novel heterocyclic analogues of bergenin as anti-mitotic agents: Design, synthesis, biological evaluation and molecular docking study

In continuation of our effort sin the development of natural product-based tubulin inhibitors with potential anti-mitotic activities, a novel bergenin hybrids incorporating sulfonate and 1, 2, 3-triazole moieties at carbon-11 were designed and synthesized. The in vitro cytotoxic activity of these derivatives ( 3a-i, 6a-k and 7a-g ) was assessed against various cancer cells and majority of derivatives in this study were shown potent anticancer activity against tested cancer cells than that parent compound. Especially, the compounds 3i, 6g , and 6h exhibited significant activity against HeLa cell line with IC 50 of 9.1 & PLUSMN; 0.4, 10 & PLUSMN; 0.2, and 7 & PLUSMN; 0.1 & mu;M, which is comparable to the standard drug, nocodazole (IC 50 5.2 & PLUSMN; 1.3 & mu;M). The flowcytometry analysis indicated that the compounds 3i, 6g , and 6h arrest cells at G2/M phase and increased expression of mitotic markers, Cyclin B1 and PLK1 proteins. In addition, 3i, 6g , and 6h generate the oxidative stress and induce apoptosis in the HeLa cells was confirmed with flowcytometry analysis. Molecular docking studies revealed that the compounds 3i, 6g , and 6h have significant binding energy with PLK1 and Cyclin B1 protein and regulating the apoptotic process. & COPY; 2023 Elsevier B.V. All rights reserved.