title: Synthesis and antiproliferative activity of substituted 3[2-(1H-indol-3-yl)- 1,3-thiazol-4-yl]-1H-pyrrolo[3,2-b]pyridines, marine alkaloid nortopsentin analogues.
abstract: A large number of indolyl-4-azaindolyl thiazoles, nortopsentin analogues, were conveniently synthesized. The antiproliferative activity of the new derivatives was examined against four human tumor cell lines with different histologic origin. Seven derivatives consistently reduced the growth of the experimental models independently of TP53 gene status and exhibited the highest activity against the malignant peritoneal mesothelioma (STO) cell line. The most active compound of this series acts as a CDK1 inhibitor, and was found to cause cell cycle arrest at G2/M phase, to induce apoptosis by preventing the phosphorylation of survivin in Thr(34) and to increase the cytotoxic activity of paclitaxel in STO cells.
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: M
authors.initials: M
authors.lastname: Pennati
authors.forename: P
authors.initials: P
authors.lastname: Barraja
authors.forename: A
authors.initials: A
authors.lastname: Montalbano
authors.forename: B
authors.initials: B
authors.lastname: Parrino
authors.forename: V
authors.initials: V
authors.lastname: Spanò
authors.forename: A
authors.initials: A
authors.lastname: Lopergolo
authors.forename: S
authors.initials: S
authors.lastname: Sbarra
authors.forename: V
authors.initials: V
authors.lastname: Doldi
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: G
authors.initials: G
authors.lastname: Cirrincione
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, STEBICEF, via Archirafi 32, 90123 Palermo, Italy. patrizia.diana@unipa.it.
authors.forename: P
authors.initials: P
authors.lastname: Diana
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines