Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds

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• 作者：Ju-feng Sun ; Gui-ge Hou ; Feng Zhao ; Wei Cong ; Hong-juan Li ; Wen-shuai Liu and Chunhua Wang
• 刊名：Chemical Biology & Drug Design
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：88
• 期：4
• 页码：534-541
• 全文大小：743K
• ISSN：1747-0285

文摘

A series of heterocyclic α,β-unsaturated carbonyl compounds (1a-1d, 2a-2d, 3a-3d, 4a-3d, and 5a-5d) with 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore were synthesized for the development of anticancer and multidrug resistance reverting agents. The antiproliferative activities were tested against nine human cancer cell lines. Approximately 73% of the IC₅₀ values were below 5 μm, while 35% of these figures were submicromolar, and compounds 3a-3d with 4-trifluoro methyl in the arylidene benzene rings were the most potent, since their IC₅₀ values are between 0.06 and 3.09 μm against all cancer cell lines employed. Meanwhile, their multidrug resistance reversal properties and cellular uptake were further examined. The data displayed that all of these compounds could reverse multidrug resistance, particularly, compounds 3a and 4a demonstrated both potent multidrug resistance reverting properties and strong antiproliferative activities, which can be taken as leading molecules for further research of dual effect agents in tumor chemotherapy.