3-[4-(1H-Indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, Nortopsentin Analogues with Antiproliferative Activity

• Main Authors: Barbara Parrino, Anna Carbone, Gloria Di Vita, Cristina Ciancimino, Alessandro Attanzio, Virginia Spanò, Alessandra Montalbano, Paola Barraja, Luisa Tesoriere, Maria Antonia Livrea, Patrizia Diana, Girolamo Cirrincione
• Format: Article
• Language: English
• Published: MDPI AG 2015-04-01
• Series: Marine Drugs
• Subjects: marine alkaloids; indolyl alkaloids; nortopsentin analogues; 3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines; antiproliferative activity
• Online Access: http://www.mdpi.com/1660-3397/13/4/1901

A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase.