The main metabolic pathway of oracin, a new potential cytostatic drug, in human liver microsomes and cytosol: stereoselectivity of reoxidation of the principal metabolite 11-dihydrooracin to oracin.

Abstract

Chirality is a prominent feature of most biological processes. The intrinsic asymmetry of receptors, enzymes, and other endogenous macromolecules represents the basis for biological discrimination between the stereoisomeric forms of all foreign compounds in organism. Stereoselectivity and stereospecificity, two principal chiral attributes of enzyme activity, play important role in biotransformation process of drugs and other xenobiotics. The stereospecificity of enzymes leads to the preferential formation of certain enantiomer, the stereoselectivity of enzymes, on the other hand, expresses the preference of one stereoisomer form of substrate for subsequent biotransformation. An approach to the study of different conditions for the formation of the two enantiomers of principal metabolite of potential cytostatic drug oracin in Man in vitro is described. The futile cycle, in which the principal metabolite is converted to the parent drug, is also discussed. The results emphasise the fact that the stereospecificity of enzymes in Man is often distinct from other laboratory species studied.