Synthesis and biological evaluation of new penta- and heptacyclic indolo- and quinolinocarbazole ring systems obtained via Pd(0) catalysed reductive N-heteroannulation.

Date publication

octobre 2010

Auteurs

Membres identifiés du Cancéropôle Est :
Dr NUZILLARD Jean-Marc , Pr SAPI Janos , Dr BRASSART Bertrand , Dr COCHARD Marie

Tous les auteurs :
Laronze-Cochard M, Cochard F, Daras E, Lansiaux A, Brassart B, Vanquelef E, Prost E, Nuzillard JM, Baldeyrou B, Goosens JF, Lozach O, Meijer L, Riou JF, Henon E, Sapi J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/20734015

Résumé

A short route, involving a tetramolecular condensation reaction and a Pd/C catalyst-H(2)-mediated reductive N-heteroannulation as the key-steps, has been found for the synthesis of some new penta- and heptacyclic indolo- (12), quinolino- (13) and indoloquinolinocarbazole (11) derivatives. HF-DFT (B3LYP) energy profiles and NMR calculations were carried out to help in the understanding of the experimental results. N-Alkylated indoloquinolinocarbazoles (16b, 17a, 17b and 18) were prepared and screened essentially toward some cancer-(G-quadruplex, DNA, topoisomerase I) and CNS-related (kinases) targets. Biological results evidenced 13 as a potent CDK-5 and GSK-3beta kinases inhibitor, while di- or triaminopropyl-substituted indoloquinolinocarbazoles 17b or 18 targeted rather DNA-duplex or telomeric G-quadruplex structures, respectively.

Référence

Org Biomol Chem. 2010 Oct 21;8(20):4625-36