Use of In Vitro and Predictive In Silico Models to Study the Inhibition of Cytochrome P4503A by XXXX .

@entity1 @entity51893 @entity251 @entity3884 @entity5322 @entity35 @entity4025 @entity4975
UNASSIGNED: @entity5322 is recognized as the main enzyme involved in the metabolism of drugs and xenobiotics in the @entity1 body and its inhibition may lead to undesirable consequences. @entity51893 , including @entity4025 , belong to a group of dietary health-promoting compounds that also act as inhibitors of @entity5322 . The aim of this study was to examine the use of computer modeling of enzyme-ligand interactions to analyze and predict the inhibition of structurally related compounds. To this end, an @entity4975 group was attached to @entity4025 and the interactions of @entity5322 with @entity4025 , its @entity4975 analogue (RA) and a known synthetic inhibitor were studied and compared in two biological models. Specifically, the metabolism of @entity251 was examined in a @entity1 intestine cell line (Caco-2/TC7) and in @entity35 liver microsomes (RLM). The results demonstrated a weak inhibitory effect of RA on @entity5322 , as compared to @entity4025 itself, in both biological models. @entity1 @entity5322 was more susceptible to inhibition than the commonly used model isozyme from @entity35 . Modeling of the binding site of @entity5322 revealed a combination of three types of interactions: hydrophobic interactions, electrostatic interactions and @entity3884 bonds. A docking simulation revealed that the RA lacked an important binding feature, as compared to @entity4025 , and that that difference may be responsible for its lower level of affinity for @entity5322 . Software analysis of binding affinity may serve as a predictive tool for designing new therapeutic compounds in terms of inhibition of @entity5322 and help to reveal the biochemical nature of the interactions of dietary compounds, herbal compounds and drugs whose metabolism is mediated by this enzyme.
