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

被引：49

作者：

Carbone, A. ^{[1
]}

Pennati, M. ^{[2
]}

Barraja, P. ^{[1
]}

Montalbano, A. ^{[1
]}

Parrino, B. ^{[1
]}

Spano, V. ^{[1
]}

Lopergolo, A. ^{[2
]}

Sbarra, S. ^{[2
]}

Doldi, V. ^{[2
]}

Zaffaroni, N. ^{[2
]}

Cirrincione, G. ^{[1
]}

Diana, P. ^{[1
]}

机构：

[1] STEBICEF, Dipartimento Sci & Tecnol Biol Chim & Farmaceut, I-90123 Palermo, Italy

[2] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Mol Pharmacol Unit, I-20133 Milan, Italy

来源：

CURRENT MEDICINAL CHEMISTRY | 2014年 / 21卷 / 14期

关键词：

Antiproliferative activity; CDK1; inhibitors; diffuse malignant peritoneal mesothelioma; indolyl-4-azaindolyl thiazoles; nortopsentin analogues; survivin; CYTOTOXICITY EVALUATION; BIS(INDOLE) ALKALOIDS; BISINDOLE ALKALOIDS; ANTITUMOR-ACTIVITY; NATURAL-PRODUCTS; RING-SYSTEM; SPONGE; FLAVOPIRIDOL; SURVIVIN; DERIVATIVES;

D O I：

10.2174/09298673113206660307

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 G(2)/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.

引用

页码：1654 / 1666

页数：13

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