Entamoeba histolytica: inhibition of malic enzyme and alcohol dehydrogenase by (ñ)-,(+)-,and (-)- gossypol

RESUMO

Gossypol, a natural racemic mixture with action on NADP- and NAD-oxidoreductases from diverse species, has been proposed as a possible antiamebic medication considering several of its pharmacological properties. In this study it was found that malic enzyme and alcohol dehydrogenase from Entamoeba histolytica are strongly inhibited by (ñ)-gossypol, and both (+)- and (-)- enantiomers. The inhibition was of the noncompetitive type among their respective substrates in all cases. The (ñ)-, (+)-, (-)-gossypol half-maximal inhibitory concentrations (IC 50) for the malic enzyme were 3.71, 13.37 and 1.03 µM, and againts the alcohol dehydrogenase 79.64, 124.43 and 42.56 µM, respectively. Therefore, the (-) enantiomer resulted 3.6 and 13.0 times more potent than the racemic mixture and (+)- gossypol, respectively, to inhibit the malic enzyme, and 1.9 times and 2.9 times more potent than the racemic mixture and (+)-gossypol, respectively, against the alcohol dehydrogenase. Accordingly, one possible mechanism of the antiamebic affect of gossypol could be the inhibition of vital NADP-dependent enzymes as those analyzed in this study