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 (IC
50
= 13.5 μM) and potent antiproliferative activity (IC
50
values: 0.65 μM∼0.90 μM).
G13
potently inhibited the migration and invasion of MDA-MB-231 cells, and displayed potent antiangiogenic activity. It efficiently increased intracellular ROS level and decreased MMP in cancer cells, and obviously induced the fragmentation and disassembly of the microtubules network. More importantly,
G13
exhibited good
in vivo
antitumour efficacy in MDA-MB-231 xenograft model (TGI = 38.2%; i.p., 30 mg/kg).
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