Boucle Sebastien, Melin Celine, Clastre Marc, Guillard Jerome
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
University François Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales, 31 avenue Monge, 37200 Tours, France.
Mar Drugs. 2015 Jan 19;13(1):655-65. doi: 10.3390/md13010655.
This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1-11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.
本文描述了一种源自玫瑰树碱和海洋生物碱马卡鲁胺A的新型杂环杂化物的合成及生物学评价。通过七步反应得到了吡啶并喹喔啉二酮12，总产率为6.5%。对12及其中间体1 - 11进行了针对不同癌细胞系的体外细胞毒性活性评价，并测试了它们对人DNA拓扑异构酶II的抑制活性。电泳分析表明，五元环12在100 μM时像阿霉素一样抑制拓扑异构酶II。发现化合物9具有有趣的特性，对Caco - 2、HCT - 116、Pc - 3和NCI细胞系的细胞毒性分别为15、15、15和10 μM，对人成纤维细胞没有明显毒性。
Zotero 插件
