cis-Restricted 3-Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays
详细信息 查看全文
- 作者：Dmitry V. Tsyganov ; Leonid D. Konyushkin ; Irina B. Karmanova ; Sergei I. Firgang ; Yuri A. Strelenko ; Marina N. Semenova ; Alex S. Kiselyov ; Victor V. Semenov
- 刊名：Journal of Natural Products
- 出版年：2013
- 出版时间：August 23, 2013
- 年：2013
- 卷：76
- 期：8
- 页码：1485-1491
- 全文大小：316K
- 年卷期：v.76,no.8(August 23, 2013)
- ISSN：1520-6025
文摘
We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells.