(−)-Gossypol: An active male antifertility agent

Resolution of gossypol: Analytical and preparative HPLC

“…The implication that (-)-gossypol is the active enantiomer has led to a search for plants producing this isomer (none has so far been reported) and to investigations of methodsforthe resolution ofthe racemate. We have found that gossypol can be resolved by conversion to diastereomeric SchiWs base derivatives using a chiral amine followed by preparative HPLC separation on a chiral amino acid bonded phase and that (-)-gossypol is indeed an active, oral antifertility agent [16]. As a consequence, there is likely to be an increasing focusing of attention on the (-)-enantiomer of gossypol in future antifertility studies with this compound.…”

Cytotoxicity of enantiomers of gossypol

“…Gossypol, when extracted from the cotton plant, is a mixture of (+) and (-) enantiomers which have now been separated (Matlin & Zhou, 1984). Since it has been shown that the (-) enantiomer of gossypol is more effective than the racemic mixture in producing infertility in male hamsters (Matlin et al, 1985), this led us to examine the cytotoxicity of the enantiomers and the racemic mixture on normal and tumour-derived cells in culture. The (-) Table I shows the effect of racemic gossypol on a number of cell types in terms of the concentration that brought about a 50% reduction in cell proliferation over a 3 day period.…”

Inhibition of testicular LDH-X from laboratory animals and man by gossypol and its isomers

“…In all but one experiment there is no suggestion of increased potency of any gossypol sample or isomer on the inhibition of LDH-X in vitro. How¬ ever ( -)-gossypol was slightly more potent upon hamster LDH-X when a-ketobutyrate was the substrate and it is this isomer that is believed to possess more potent antifertility activity (Matlin et al, 1985). In general these results provide evidence to suggest that LDH-X inhibition in vivo is not a primary contribution to the antifertility effect produced by gossypol, especially since LDH-X inhibition in vitro is produced by the ( + )-isomer which lacks antifertility properties ¡Waller Matlin et al, 1985).…”

“…In spite of this clinical application the antifertility mechanism remains unknown. Recent experiments suggest that the antifertility properties of gossypol are associated specifically with the ( -)-isomer (Waller et al, 1983;Matlin et al 1985). The apparent selectivity of gossypol towards mature and developing spermatozoa suggests that they possess a unique target.…”

“…This paper describes the interaction of gossypol with LDH-X prepared from the testes of a variety of species, susceptible and unsusceptible, to the antifertility effects of gossypol and attempts to try and elucidate the importance of the in-vitro inhibition. (Matlin et al, 1985 (1982) and stored in liquid nitrogen until required for assay. Serum from men and adult hamsters was also prepared as a source of the other LDH-isoenzymes.…”