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

Author(s): A. Carbone, M. Pennati, P. Barraja, A. Montalbano, B. Parrino, V. Spano, A. Lopergolo, S. Sbarra, V. Doldi, N. Zaffaroni, G. Cirrincione, P. Diana.

Journal Name: Current Medicinal Chemistry

Volume 21 , Issue 14 , 2014


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 Thr34 and to increase the cytotoxic activity of paclitaxel in STO cells.

Keywords: Antiproliferative activity, CDK1 inhibitors, diffuse malignant peritoneal mesothelioma, indolyl-4-azaindolyl thiazoles, nortopsentin analogues, survivin.

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Article Details

Year: 2014
Page: [1654 - 1666]
Pages: 13
DOI: 10.2174/09298673113206660307
Price: $65

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