title: Entamoeba histolytica: inhibition of malic enzyme and alcohol dehydrogenase by (+/- )-, (+)-, and (-)- gossypol.
abstract: 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 (+/-)-gossypol, and both (+)- and (-)- enantiomers. The inhibition was of the noncompetitive type among their respective substrates in all cases. The (+/-), (+)-, (-)-gossypol half-maximal inhibitory concentrations (IC50) for the malic enzyme were 3.71, 13.37 and 1.03 microM, and against the alcohol dehydrogenase 79.64, 124.43 and 42.56 microM, 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 effect of gossypol could be the inhibition of vital NADP-dependent enzymes as those analyzed in this study.
authors.affiliation: Unidad de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, N. L.
authors.forename: M T
authors.initials: MT
authors.lastname: González-Garza
authors.forename: S A
authors.initials: SA
authors.lastname: Matlin
authors.forename: B D
authors.initials: BD
authors.lastname: Mata-Cárdenas
authors.forename: S
authors.initials: S
authors.lastname: Said-Fernández
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000563:Amebicides / Q000494:pharmacology; D000818:Animals; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000201:enzymology; D006072:Gossypol / Q000737:chemistry / Q000494:pharmacology*; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
chemical_list: D000563:Amebicides; D000426:Alcohol Dehydrogenase; D008291:Malate Dehydrogenase; C031917:malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+); D006072:Gossypol