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

Marine Drugs

Barbara Parrino¹  Anna Carbone¹  Gloria Di Vita¹  Cristina Ciancimino¹  Alessandro Attanzio¹  Virginia Spanò¹  Alessandra Montalbano¹  Paola Barraja¹  Luisa Tesoriere¹  Maria Antonia Livrea¹  Patrizia Diana¹  Girolamo Cirrincione² 

[1] Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy;

关键词: marine alkaloids;    indolyl alkaloids;    nortopsentin analogues;    antiproliferative activity;   

DOI  :  10.3390/md13041901

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.