Design, synthesis and evaluation of dihydro-1H-indene derivatives as novel tubulin polymerisation inhibitors with anti-angiogenic and antitumor potency.

ABSTRACT: Angiogenesis plays an important role in tumour generation and progression, which is used to supply nutrients and metastasis. Herein, a series of novel dihydro-1H-indene derivatives were designed and evaluated as tubulin polymerisation inhibitors by binding to colchicine site, exhibiting anti-angiogenic activities against new vessel forming. Through structure-activity relationships study, compound 12d was found to be the most potent derivative possessing the antiproliferative activity against four cancer lines with IC₅₀ values among 0.028-0.087 µM. Compound 12d bound to colchicine site on tubulin and inhibited tubulin polymerisation in vitro. In addition, compound 12d induced cell cycle arrest at G2/M phase, stimulated cell apoptosis, inh

SUBMITTER: Xu S 

PROVIDER: S-EPMC10438863 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature