Chem. Pharm. Bull., 52(5),540-545, May 2004

Regular Articles

Synthesis and Cytotoxic Activity of Pyranocarbazole Analogues of Ellipticine and Acronycine

Hong Anh TRAN-THI,^a Thuan NGUYEN-THI,^a Sylvie MICHEL,^a Francois TILLEQUIN,^a Michel KOCH,^a Bruno PFEIFFER,^b Alain PIERRÉ,^c and Hanh TRINH-VAN-DUFAT^*,a

^a Laboratoire de Pharmacognosie de l'Université René Descartes, U.M.R./C.N.R.S. N° 8638, Faculté des Sciences Pharmaceutiques et Biologiques; 4 Avenue de l'Observatoire, 75006 Paris, France: ^b Les Laboratoires Servier, and Institut de Recherches Internationales Servier; 1 rue Carle Hébert, 92415 Courbevoie Cedex, France: and ^c Division Recherche Cancérologie, 125 Chemin de Ronde; 78290 Croissy sur Seine, France. * To whom correspondence should be addressed. e-mail: dufat@pharmacie.univ-paris5.fr

Various 2,2,5,11-tetramethyl- and 2,2,5,6,11-pentamethyl-2,6-dihydropyrano[3,2-b]carbazole derivatives were synthesized by condensation of 3-methylbut-2-enal or 3-chloro-3-methylbut-1-yne with an appropriate hydroxycarbazole. These compounds associate the tricyclic system responsible for the intercalating properties of ellipticine related drugs, with the dimethylpyran pharmacophore of acronycine derivatives. The study of the biological properties of the new pyrano[3,2-b]carbazole derivatives was carried out in vitro on L1210 murine leukaemia cell line. The three (±)-cis-diol diesters 15, 16, and 18 were the most active compounds.

Key words ellipticine; acronycine; 2,6-dihydropyrano[3,2-b]carbazole; cytotoxicity