Modulation of P-Glycoprotein activity: Insights from docking studies

RJ Ferreira; M Reis; MMM Santos; J Molnár; DJVA dos Santos; MJU Ferreira

doi:10.1055/s-0032-1320395

Planta Medica, Table of Contents

Modulation of P-Glycoprotein activity: Insights from docking studies

RJ Ferreira ¹, M Reis ¹, MMM Santos ¹, J Molnár ², DJVA dos Santos ¹, MJU Ferreira ¹

¹Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisboa, Portugal
²Department of Medical Microbiology and Immunobiology, University of Szeged, Szeged, Hungary

Abstract

P-glycoprotein is one of the best studied transmembranar proteins directly related with multidrug resistance phenomenon. Using a refined P-gp structure recently published by our group, new docking studies have identified three distinct binding sites: two for substrates (H- and R-sites) and one for modulators (Modulator-site), which are in perfect agreement with experimental studies described in literature. From these docking studies, it was observed that the acylation pattern at the pentacyclic ring of lathyrane-type macrocyclic diterpenes influences the affinity towards the Modulator-site.