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Le Gossypol et ses nouveaux dérivés:Synthèse et étude d'Activités Biologiques

Abstract : Gossypol and new derivatives, synthesis and biological activities Abstract : New Schiff bases of racemic gossypol and gossypolone and of (+)- or (-)-gossypol enantiomers are described. Schiff bases obtained from gossypol enantiomers are optically stable at room temperature whereas gossypolone Schiff bases racemize quickly and may be observed only at lower temperatures. Their cytotoxic activities on KB human cancer cells were determined : the methylimine and ethylimine derivatives of racemic gossypolone were the most active compounds, and the cytotoxicity of racemic gossypol and gossypolone was increased when the tests were performed in the absence of serum and decreased when catalase as well as mannitol were added to the culture medium. (-)-gossypol and (-)-gossypol derivatives displayed higher toxicities on KB and MCF7 cells than the corresponding (+) isomers. New dithiane or dithiolane derivatives of gossypol and gossypolone were synthesized with dithiolethane or dithiolpropane in the presence of BF3/Et2O. Under the same conditions, tetramethyl or hexamethyl ethers of gossypol led to cyclic thioderivatives. These thioderivatives exhibited low toxicity on KB cells. Dithiane or dithiolane derivatives react easily with electrophiles, nitrosonium tetrafluoroborate or nitric oxide plus ferric ion, in aprotic solvents to regenerate gossypolone or to form dehydrogossypoldithiane, which display higher toxicity on KB cells. Since, the low toxicity of gossypol thioderivatives is reversed by nitric oxide donors in physiological media, it is suggested that gossypol and gossypolone dithianes and dithiolanes can be used as prodrugs that target tumor cells surrounded by high concentrations of nitric oxide.
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Contributor : Vithuy Dao <>
Submitted on : Wednesday, January 14, 2004 - 10:01:41 PM
Last modification on : Wednesday, March 17, 2021 - 2:36:02 PM
Long-term archiving on: : Friday, April 2, 2010 - 7:34:49 PM

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Vi Thuy Dao. Le Gossypol et ses nouveaux dérivés:Synthèse et étude d'Activités Biologiques. Sciences du Vivant [q-bio]. Université Paris Sud - Paris XI, 2002. Français. ⟨tel-00004168⟩

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