3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity

Maria Antonia Livrea, Alessandro Attanzio, Barbara Parrino, Luisa Tesoriere, Alessandra Montalbano, Paola Barraja, Virginia Spano', Patrizia Diana, Cristina Ciancimino, Gloria Di Vita, Girolamo Cirrincione, Anna Carbone, Virginia Spanò, Barbara Parrino, Alessandro Attanzio, Cristina Ciancimino, Anna Carbone, Gloria Di Vita, Alessandra Montalbano, Paola BarrajaGirolamo Cirrincione, Patrizia Diana, Luisa Tesoriere, Maria Antonia Livrea

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41 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1901-1924
Number of pages24
JournalMarine Drugs
Volume13
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Drug Discovery

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