Discovery of potent tubulin inhibitors targeting the colchicine binding site via structure-based lead optimization and antitumor evaluation.

ABSTRACT: The colchicine binding site of tubulin is a promising target for discovering novel antitumour agents. Previously, we identified 2-aryl-4-amide-quinoline derivatives displayed moderate tubulin polymerisation inhibitory activity and broad-spectrum in vitro antitumour activity. In this study, structure based rational design and systematic structural optimisation were performed to obtain analogues C1∼J2 bearing diverse substituents and scaffolds. Among them, analogue G13 bearing a hydroxymethyl group displayed good tubulin polymerisation inhibitory activity (IC₅₀  =  13.5 μM) and potent antiproliferative activity (IC₅₀ values: 0.65 μM∼0.90 μM). G13 potently inhibited the migration and invasion of MDA-MB-231 cells, and displayed potent antiangio

SUBMITTER: Liu W 

PROVIDER: S-EPMC9848350 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature