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

Angiogenesis plays an important role in tumour generation and progression, which is used to supply nutrients and metastasis. Herein, a series of novel dihydro-1-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 was found to be the most potent derivative possessing the antiproliferative activity against four cancer lines with IC values among 0.028-0.087 M. Compound bound to colchicine site on tubulin and inhibited tubulin polymerisation . In addition, compound induced cell cycle arrest at G2/M phase, stimulated cell apoptosis, inhibited tumour metastasis and angiogenesis. Finally, the results of assay suggested that compound could prevent tumour generation, inhibit tumour proliferation and angiogenesis without obvious toxicity. Collectively, all these findings suggested that compound is a novel tubulin polymerisation inhibitor deserving further research.