3-[4-(1H-Indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines,Nortopsentin Analogues with Antiproliferative Activity |
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| 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 |
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| Affiliation: | Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy; E-Mails: (B.P.); (A.C.); (G.D.); (C.C.); (A.A.); (V.S.); (A.M.); (P.B.); (L.T.); (M.A.L.); (P.D.) |
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| 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. |
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| Keywords: | 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 |
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