Study of Some Piperine Analogues on Drugs Efflux by Targeting P-glycoprotein, an in silico Approach

Background: P-glycoprotein (P-gp) is the most important member of adenosine triphosphate (ATP) binding cassette (ABC) family and plays a critical role in facilitating the efflux mechanism to extrude various drug molecules. It is mostly present in pancreas, kidney, ovary, liver and breast. Piperine is a well known inhibitor of P-gp mediated efflux mechanism that makes it an efficient enhancer for promoting the bioavailability of a number of compounds against various diseases. Objective: The aim of present work is to predict potency of some piperine analogues as inhibitors of P-gp mediated efflux process and enhancer of drugs bioavailability in human and bacterial P-gps using in silico approach. Methods: Many computational approaches like protein modeling, molecular docking simulation and pharmacophore studies have been used in order to explore the prediction of protein ligand interaction and their inhibition. Result: In the present work, the surrounding residues of ATP binding site together with the binding affinity of piperine analogues have been observed for human and bacterial P-gps. This leads to the characterization of few piperine analogues as having higher potency than ATP for inhibiting the efflux process and enhancing bioavailability of drugs. Conclusion: This study is likely to help in designing more potent novel candidates which might be useful as efflux inhibitors and bioavailability enhancers for many pharmaceutically important drug molecules.