Synthesis, biological evaluation and molecular docking studies of trans-indole-3-acrylamide derivatives, a new class of tubulin polymerization inhibitors

被引：51

作者：

Baytas, Sultan Nacak ^{[1
]}

Inceler, Nazan ^{[1
]}

Yilmaz, Akin ^{[2
]}

Olgac, Abdurrahman ^{[1
]}

Menevse, Sevda ^{[2
]}

Banoglu, Erden ^{[1
]}

Hamel, Ernest ^{[3
]}

Bortolozzi, Roberta ^{[4
]}

Viola, Giampietro ^{[4
]}

机构：

[1] Gazi Univ, Div Pharmaceut Sci, Dept Pharmaceut Chem, Fac Pharm, TR-06330 Ankara, Turkey

[2] Gazi Univ, Dept Med Biol & Genet, Fac Med, TR-06500 Ankara, Turkey

[3] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA

[4] Univ Padua, Dept Womens & Childrens Hlth, Lab Oncohematol, I-35128 Padua, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 12期

关键词：

Synthesis; Anticancer activity; Indole; Tubulin polymerization; Colchicine binding; Apoptosis; Cell cycle arrest; Molecular docking; RAPID COLORIMETRIC ASSAY; ANTIMITOTIC AGENTS; CHALCONES; ANALOGS; COLCHICINE; GROWTH; CHEMISTRY; SURVIVAL; DESIGN; CELLS;

D O I：

10.1016/j.bmc.2014.04.027

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：

In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a-k) and investigated their activity for inhibition of cell proliferation against five human cancer cell lines (HeLa, MCF7, MDA-MB-231, Raji and HL-60) by MTT assay. Compound 3e showed significant antiproliferative activity against both the Raji and HL-60 cell lines with IC50 values of 9.5 and 5.1 mu M, respectively. Compound 3e also exhibited moderate inhibitory activity on tubulin polymerization (IC50 = 17 mu M). Flow cytometric analysis of cultured cells treated with 3e also demonstrated that the compound caused cell cycle arrest at the G2/M phase in HL-60 and HeLa cells. Moreover, 3e, the most active compound, caused an apoptotic cell death through the activation of caspase-3. Docking simulations suggested that 3e binds to the colchicine site of tubulin. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：3096 / 3104

页数：9

共 47 条

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