Pyrazolone-fused combretastatins and their precursors: synthesis, cytotoxicity, antitubulin activity and molecular modeling studies

被引：51

作者：

Burja, Bojan ^{[1
]}

Cimbora-Zovko, Tamara ^{[2
]}

Tomic, Sanja ^{[3
]}

Jelusic, Tihana ^{[2
]}

Kocevar, Marijan ^{[1
]}

Polanc, Slovenko ^{[1
]}

Osmak, Maja ^{[2
]}

机构：

[1] Univ Ljubljana, Fac Chem & Chem Technol, SI-1000 Ljubljana, Slovenia

[2] Rudjer Boskovic Inst, Div Mol Biol, HR-10000 Zagreb, Croatia

[3] Rudjer Boskovic Inst, Div Phys Chem, HR-10000 Zagreb, Croatia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 07期

关键词：

Combretastatin CA-4 derivatives; Cytotoxicity; Tubulin; Molecular modeling; BIOLOGICAL-ACTIVITY; ANTITUMOR-ACTIVITY; A-4; ANALOGS; DERIVATIVES; DESIGN; POTENT; CIS; PYRAZOL-3-ONES; COLCHICINE; CHEMISTRY;

D O I：

10.1016/j.bmc.2010.03.006

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 series of pyrazolone-fused combretastatins and precursors were synthesized and their cytotoxicity as well as antitubulin potential was evaluated. The hydrazide 9f and the pyrazolone-fused combretastatins 12a, 12b and 12c were highly cytotoxic against various tumor cell lines including cisplatin resistant cells. The same compounds were also the best inhibitors of tubulin polymerization. Molecular modeling results showed that they bind the colchicine binding site at the tubulin heterodimer. The hydrazide 9f arrested HeLa cells in the G2/M phase of the cell cycle and strongly affected cell shape and microtubule network. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2375 / 2387

页数：13

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