Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency

被引：8

作者：

Boucle, Sebastien ^{[1
,2
]}

Melin, Celine ^{[3
]}

Clastre, Marc ^{[3
]}

Guillard, Jerome ^{[4
]}

机构：

[1] Emory Univ, Sch Med, Biochem Pharmacol Lab, Dept Pediat,Ctr AIDS Res, Decatur, GA 30033 USA

[2] Vet Affairs Med Ctr, Decatur, GA 30033 USA

[3] Univ Tours, Biomol & Biotechnol Veget EA2106, F-37200 Tours, France

[4] Univ Poitiers, UMR CNRS IC2MP 7285, F-86022 Poitiers, France

来源：

MARINE DRUGS | 2015年 / 13卷 / 01期

关键词：

makaluvamine; pyrroloiminoquinone; marine drugs analogues; topoisomerase II inhibitor; antitumor activity; NATURAL-PRODUCTS; TOPOISOMERASE-II; MAKALUVAMINES;

D O I：

10.3390/md13010655

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 mu M. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 mu M against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

引用

页码：655 / 665

页数：11

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