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

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 e...

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Bibliographic Details
Published in:	Current medicinal chemistry Vol. 21; no. 14; p. 1654
Main Authors:	Carbone, A, Pennati, M, Barraja, P, Montalbano, A, Parrino, B, Spanò, V, Lopergolo, A, Sbarra, S, Doldi, V, Zaffaroni, N, Cirrincione, G, Diana, P
Format:	Journal Article
Language:	English
Published:	United Arab Emirates 2014
Subjects:	Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Apoptosis - drug effects Cell Line Cell Proliferation - drug effects Humans Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - pharmacology Pyridines - chemical synthesis Pyridines - pharmacology Structure-Activity Relationship
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Summary:	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.
ISSN:	1875-533X
DOI:	10.2174/09298673113206660307