Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization.

ABSTRACT:

Aim

Discovery of novel series of colchicine binding site inhibitors (CBSIs).

Materials & methods

Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.7c, 7e and 11a were more potent than colchicine with IC₅₀ of 0.09, 0.05 and 0.06 μM, and percentage inhibition in tubulin polymerization of 95.2, 96.0 and 96.3%, respectively. Compounds 7c and 11a showed cell-cycle arrest at G2/M phase and induced apoptosis and were able to bind the colchicine binding site of tubulin with comparable affinity to colchicine. Docking study

SUBMITTER: Moussa SA 

PROVIDER: S-EPMC6479276 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature