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The Metabolic Fate of iso Combretastatin A‐4 in Human Liver Microsomes: Identification, Synthesis and Biological Evaluation of Metabolites

2011; Wiley; Volume: 6; Issue: 10 Linguagem: Inglês

10.1002/cmdc.201100193

1860-7187

Mohamed Ali Soussi, Silvio Aprile, Samir Messaoudi, Olivier Provot, Erika Del Grosso, Jérôme Bignon, Joëlle Dubois, Jean‐Daniel Brion, Giorgio Grosa, Mouâd Alami,

Biochemical and Molecular Research

Digesting drugs! Due to the structural differences between isocombretastatin A-4 (isoCA-4) bearing a 1,1-diarylethylene scaffold and the natural Z-stilbene combretastatin A-4 (CA-4), we examined the metabolic profile of isoCA-4 using human liver fractions. Seven isoCA-4 metabolites, resulting from O-demethylation, hydroxylation of the aromatic rings were identified and synthesized. Evaluation of their cytotoxicity and their ability to inhibit tubulin polymerization (ITP activity) led us to identify a metabolite with a strong antimitotic activity comparable to that of isoCA-4. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.