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

Sébastien Bouclé (1) , Céline Melin (2) , Marc Clastre (2) , Jerome Guillard (3)

1 GICC UMR 7292 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017]
2 BBV - Biomolécules et biotechnologies végétales
3 IC2MP [Poitiers] - Institut de chimie des milieux et matériaux de Poitiers [UMR 7285]

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.

Mots clés: antitumor activity; marine drugs analogues; topoisomerase II inhibitor; makaluvamine; pyrroloiminoquinone

Domaines: Catalyse

Sébastien Bouclé, Céline Melin, Marc Clastre, Jerome Guillard. Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency. Marine drugs, 2015, 13, pp.655-665. ⟨10.3390/md13010655⟩. ⟨hal-01330387⟩