Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents.

08:00 EDT 6th April 2019 | BioPortfolio

Summary of "Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents."

Further optimization of the trimethoxyphenyl scaffold of parent chalcone compound (2a) by introducing a pyridine ring afforded a series of novel pyridine-chalcone derivatives as potential anti-tubulin agents. All the target compounds were evaluated for their antiproliferative activities. Among them, representative compound 16f exhibited the most potent activity with the IC values ranging from 0.023 to 0.045 μM against a panel of cancer cell lines. Further mechanism study results demonstrated that compound 16f effectively inhibited the microtubule polymerization by binding to the colchicine site of tubulin. Moreover, cellular mechanism studies disclosed that 16f caused G2/M phase arrest, induced cell apoptosis and disrupted the intracellular microtubule network. Also, 16f reduced the cell migration and disrupted the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Importantly, 16f significantly inhibited tumor growth in H22 xenograft models without apparent toxicity, which was stronger than the reference compound CA-4, indicating that it is worthy to investigate 16f as a potent microtubule-destabilizing agent for cancer therapy.


Journal Details

This article was published in the following journal.

Name: European journal of medicinal chemistry
ISSN: 1768-3254
Pages: 1-14


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