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

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• 作者：Bojan Burja ; Tamara &#x10c ; imbora-Zovko ; Sanja Tomi&#x107 ; Tihana Jeluš ; i&#x107 ; Marijan Ko&#x10d ; evar ; Slovenko Polanc ; Maja Osmak
• 关键词：Combretastatin CA-4 derivatives ; Cytotoxicity ; Tubulin ; Molecular modeling
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：1 April 2010
• 年：2010
• 卷：18
• 期：7
• 页码：2375-2387
• 全文大小：1383 K

文摘

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.