Inhibition of lactate dehydrogenase-X by imino-derivatives of gossypol:structure activity relationship.
Six imino-derivatives (II, III, IV, V, VI, VII) of gossypol (I) have been synthesized, and their effects were evaluated on the purified mouse lactate dehydrogenase-X. Three of these derivatives (V, VI, VII) with aldehyde groups substituted with hydrophobic functionalities showed equivalent or more inhibitory effects on lactate dehydrogenase-X than gossypol, whereas three other derivatives (II, III, IV) with aldehyde groups substituted with hydrophilic functional groups lost the ability to inhibit lactate dehydrogenase-X. It is suggested that two aldehyde groups of gossypol are not essential to inhibit lactate dehydrogenase-X. Furthermore, the hydrophobic property of the gossypol molecule seems to play a more important role in inhibiting lactate dehydrogenase-X. Therefore, lactate dehydrogenase-X inhibition by gossypol may not be associated with its antifertility mechanism, because the aldehyde group of gossypol is known to be required for its antifertility effect.
D000818:Animals; D006072:Gossypol / Q000031:analogs & derivatives / Q000494:pharmacology*; D007097:Imines / Q000494:pharmacology*; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013329:Structure-Activity Relationship; D013737:Testis / Q000201:enzymology
D007097:Imines; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D006072:Gossypol