Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of dipyrrolo[3,4-a:3,4-c]carbazole triones.

Elisabeth Conchon (1) , Fabrice Anizon (1) , R. Golsteyn , S. Leonce , Bruno Pfeiffer , Michelle Prudhomme (1)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique

The syntheses of dipyrrolo[3,4-a:3,4-c]carbazole-1,4,6-triones and dipyrrolo[3,4-a:3,4-c]carbazole-3,4,6-triones are reported. These compounds can be considered as granulatimide analogues in which a maleimide replaces the imidazole moiety and a five-membered lactam ring replaces the upper maleimide. The Chk1 inhibitory properties of the more soluble compounds have been evaluated and their in vitro antiproliferative activities toward three tumor cell lines: murine leukemia L1210, and human colon carcinoma HT29 and HCT116. Due to their insolubility, the biological activities of the other compounds in this series could not be evaluated. All the tested compounds proved to be potent Chk1 inhibitors

Mots clés: Granulatimide; Dipyrrolo[3; 4-a:3; 4-c]carbazole-1; 6-trione; 4-c]carbazole-3; Antitumor agents; Chk1 inhibitors

Domaines: Chimie organique

Elisabeth Conchon, Fabrice Anizon, R. Golsteyn, S. Leonce, Bruno Pfeiffer, et al.. Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties of dipyrrolo[3,4-a:3,4-c]carbazole triones.. Tetrahedron, 2006, 62, pp.11136-11144. ⟨10.1016/j.tet.2006.09.027⟩. ⟨hal-00119566⟩