title: New thioderivatives of gossypol and gossypolone, as prodrugs of cytotoxic agents.
abstract: New dithiane or dithiolane derivatives of gossypol and gossypolone were synthesized with dithiolethane or dithiolpropane in the presence of BF(3)/Et(2)O. These thioderivatives exhibited low toxicity on KB cells (human epidermoid carcinoma cells of the mouth). They react easily with electrophiles in aprotic solvents to regenerate gossypolone or to form dehydrogossypoldithianes and dehydrogossypoldithiolanes, which display higher toxicity on KB cells. In addition, the low toxicity of gossypol thioderivatives was reversed by nitric oxide donors in physiological media. These experiments suggest that gossypol and gossypolone dithianes and dithiolanes can be used as prodrugs that target tumor cells surrounded by high concentrations of nitric oxide.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif sur Yvette, France.
authors.forename: Vi-Thuy
authors.initials: VT
authors.lastname: Dao
authors.forename: Michael K
authors.initials: MK
authors.lastname: Dowd
authors.forename: Christiane
authors.initials: C
authors.lastname: Gaspard
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Martin
authors.forename: Julie
authors.initials: J
authors.lastname: Hémez
authors.forename: Olivier
authors.initials: O
authors.lastname: Laprévote
authors.forename: Michel
authors.initials: M
authors.lastname: Mayer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Michelot
mesh_terms: D045744:Cell Line, Tumor; D006072:Gossypol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D011355:Prodrugs / Q000737:chemistry / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000633:toxicity*
chemical_list: D011355:Prodrugs; D013438:Sulfhydryl Compounds; C043259:gossypolone; D006072:Gossypol