Polyalkoxy Substituted 4H-Chromenes: Synthesis by Domino Reaction and Anticancer Activity
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- 作者：Anatoliy M. Shestopalov ; Yuri M. Litvinov ; Lyudmila A. Rodinovskaya ; Oleg R. Malyshev ; Marina N. Semenova ; Victor V. Semenov
- 刊名：ACS Combinatorial Science
- 出版年：2012
- 出版时间：August 13, 2012
- 年：2012
- 卷：14
- 期：8
- 页码：484-490
- 全文大小：302K
- 年卷期：v.14,no.8(August 13, 2012)
- ISSN：2156-8944
文摘
A series of 4H-chromenes containing various modifications in the ring B and polyalkoxy substituents in the ring E has been synthesized by Knoevenagel鈥揗ichael鈥揾etero-Thorpe鈥揨iegler three-component domino reaction with the overall yield of 45鈥?2%. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antimitotic and microtubule destabilizing activity. The most active compounds 5{1,5} and 5{5,5} featured sesamol-derived ring B and m-methoxyphenyl or m-methoxymethylenedioxyphenyl ring E. Compounds 5{3,1}, 5{1,2}, 5{5,4}, 5{1,5}, and 5{5,5} exhibited strong cytotoxicity in the NCI60 human tumor cell line anticancer drug screen. Surprisingly, cell growth inhibition caused by these agents was more pronounced in the multidrug resistant NCI/ADR-RES cells than the parent OVCAR-8 cell line. The results suggest that polyalkoxy substited 4H-chromenes may prove to be advantageous for further design as anticancer agents.