Synthesis kinases inhibitory potencies and in vitro antiproliferative activity of isoindigo and 7'-azaisoindigo derivatives substituted by Sonogashira cross-coupling

Fadoua Bouchikhi (1) , Fabrice Anizon (1) , Pascale Moreau (1)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique

In the course of structure–activity relationship studies we were interested in the synthesis of isoindigo and 7′-azaisoindigo derivatives substituted at the N-1 position by a 1-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl), at the 5′-position by various chains introduced by Sonogashira cross-coupling and substituted or not at the 5-position by a bromine atom. To get an insight into the substitution pattern required for the best biological potencies, their kinase inhibitory potencies and their in vitro antiproliferative activities were evaluated. The derivatives were tested toward four protein kinases (CDK5/p25, GSK3, CK1, Dyrk1A) and their in vitro antiproliferative activity was tested against two human myeloid leukaemia cell lines (K562 and HL60).

Mots clés: Indigoids; Isoindigos; Kinase inhibitors; Antitumour agents

Domaines: Chimie organique

Fadoua Bouchikhi, Fabrice Anizon, Pascale Moreau. Synthesis kinases inhibitory potencies and in vitro antiproliferative activity of isoindigo and 7'-azaisoindigo derivatives substituted by Sonogashira cross-coupling. European Journal of Medicinal Chemistry, 2009, 44, pp.2705-2710. ⟨hal-00376885⟩