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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