Pyrazolone-fused combretastatins and their precursors: synthesis,cytotoxicity, antitubulin activity and molecular modeling studies |
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| Authors: | Bojan Burja Tamara Čimbora-Zovko Sanja Tomić Tihana Jelušić Marijan Kočevar Slovenko Polanc Maja Osmak |
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| Affiliation: | 1. Faculty of Chemistry and Chemical Technology, University of Ljubljana, A?ker?eva 5, SI-1000 Ljubljana, Slovenia;2. Division of Molecular Biology, Ru?er Bo?kovi? Institute, Bijeni?ka cesta 54, HR-10000 Zagreb, Croatia;3. Division of Physical Chemistry, Ru?er Bo?kovi? Institute, Bijeni?ka cesta 54, HR-10000 Zagreb, Croatia |
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| Abstract: | 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. |
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