title: 3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin analogues with antiproliferative activity.
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.
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. barbara.parrino@unipa.it.
authors: Barbara
authors: B
authors: Parrino
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. anna.carbone@unipa.it.
authors: Anna
authors: A
authors: Carbone
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. gloria.divita@unipa.it.
authors: Gloria
authors: G
authors: Di Vita
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. cristina.ciancimino@unipa.it.
authors: Cristina
authors: C
authors: Ciancimino
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. alessandro.attanzio@unipa.it.
authors: Alessandro
authors: A
authors: Attanzio
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. virginia.spano@unipa.it.
authors: Virginia
authors: V
authors: Spanò
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. alessandra.montalbano@unipa.it.
authors: Alessandra
authors: A
authors: Montalbano
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. paola.barraja@unipa.it.
authors: Paola
authors: P
authors: Barraja
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. luisa.tesoriere@unipa.it.
authors: Luisa
authors: L
authors: Tesoriere
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. maria.livrea@unipa.it.
authors: Maria Antonia
authors: MA
authors: Livrea
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. patrizia.diana@unipa.it.
authors: Patrizia
authors: P
authors: Diana
authors: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. girolamo.cirrincione@unipa.it.
authors: Girolamo
authors: G
authors: Cirrincione
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D016195:G2 Phase / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008745:Methylation; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles; D013844:Thiazoles