(Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies.

Journal of Medicinal Chemistry
M V Ramana ReddyE Premkumar Reddy

Abstract

Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.

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Citations

Jan 8, 2013·The Journal of Organic Chemistry·Anand Kumar PandeyPrem M S Chauhan
Oct 22, 2016·European Journal of Medicinal Chemistry·Hena Khanam Shamsuzzaman
Jan 18, 2014·Bioorganic & Medicinal Chemistry·Kurt R BrundenCarlo Ballatore
Sep 11, 2014·Organic & Biomolecular Chemistry·Pratik PalSamik Nanda
Nov 28, 2018·Anti-cancer Agents in Medicinal Chemistry·Siddiq P ShaikAhmed Kamal
Jun 8, 2021·Frontiers in Oncology·Mugahed Abdullah Hasan AlbahdeWeilin Wang

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