Title : A structure-activity relationship study on cytochrome 3A4 inhibitors: Structure and crucial features
Abstract:
Cytochromes P450 (CYP) are the main actors in the oxidation of xenobiotics and play a crucial role in drug safety, persistence, bio activation, and drug-drug/food-drug interaction. This work aims to develop Quantitative Structure-Activity Relationship (QSAR) models to predict the drug interaction with one of the most important CYP isoform, namely 3A4. Computational methods are utilized to design and develop new molecules and also to understand interaction between drugs and biological targets. In this research, a QSAR model and docking analysis was successfully used to investigate important features in CYP3A4 inhibitory effect. Validation method was performed to examine the accuracy of the results. Upon the findings of these methods, energy of interaction and total shape of the molecules were important in inhibitory effect. Docking outputs were revealed the important amino acids in CYP3A4 which are responsible in binding the inhibitors. Phe57?Asp76 Arg106 ?Arg105 ?Phe220 ?Phe108 ?Ala 370 ?Ser 119 ?Leu 482 are among these amino acids.
Key words: QSAR- CYP3A4- Docking-Ketokonazole
