Abstract
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.
Keywords: Efflux mechanism, P-glycoprotein, Piperine, Docking, Drug designing, Bioinformatics.
Graphical Abstract
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