In vitro evaluation of glucuronidation of monohydroxylated aglycones related to quantum chemically-calculated parameters

Abstract Using monohydroxylated aglycones belonging to different chemical classes, we investigated the physicochemical criteria required to predict the elimination of these molecules which are substrates of UDP-glucuronosyltransferases. These enzymes possess a low specificity, particularly towards exogenous compounds. For this purpose, we determined the kinetic constants ( V max , K m , V K ) in non-treated and 3-methylcholanthrene-treated rat liver microsomes. QSAR studies were performed with the complete neglect of differential overlap assumption relating 15 theoretical descriptors characterizing the substrates. Principal component analysis shows the distributions, different before and after induction, of experimental values used as supplementary variables for V K , especially in the case of coumarinic compounds. The results described demonstrate the usefulness of QSAR analysis in glucuronidation in order to explain the observed variance in enzymatic activity and to determine the binding forces involved (steric and electronic).