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

Marine Drugs

Sebastien Boucle³  Celine Melin¹  Marc Clastre¹  Jerome Guillard² 

[1] University François Rabelais de Tours, EA2106 Biomolécules et Biotechnologies Végétales, 31 avenue Monge, 37200 Tours, France; E-Mails:;University of Poitiers, UMR CNRS IC2MP 7285, 40 avenue du Recteur Pineau, 86022 Poitiers Cedex, France;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; E-Mail:

关键词: makaluvamine;    pyrroloiminoquinone;    marine drugs analogues;    topoisomerase II inhibitor;    antitumor activity;   

DOI  :  10.3390/md13010655

来源: mdpi

【 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 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.