Stereo-specific cytotoxic effects of gossypol enantiomers and gossypolone in tumour cell lines.

摘要: The naturally occurring compound, gossypol, has been previously used as a male oral contraceptive, for the treatment of benign gynaecological conditions and cancer patients. Long-term daily dosing with gossypol is associated minimal side effects no myelosuppression. Since exhibits atropisomerism due to restricted rotation about 2,2′ carbon bond, we have isolated l- d-isomers by Schiff's base formation using chiral amine regenerated enantiomers acid hydrolysis. proposed oxidative metabolite, gossypolone, were characterized HPLC, 1H-NMR optical rotation. cytotoxicity was assessed in cell cultures derived from melanoma, lung, breast, cervix, leukaemia MTT viability assay. gossypolone similar racemic five out six lines studied. l-enantiomer induced dose-dependent kill all mean IC50 20 μM significantly more potent than d-enantiomer gossypolone. In addition, when line exposed l-gossypol (0.5–10 μM) over 4-day period, schedule-dependent decrease observed. l-Gossypol also compared respective drugs treat patients lung leukaemia. data indicate that active cisplatin, melphalan dacarbazine two melanoma lines, cisplatin daunorubicin hydroxyurea busulphan line. Preliminary studies one showed l-isomer shrinkage, membrane blebbing DNA fragmentation, characteristics suggestive apoptotic death.