Planta Med 2012; 78 - PD37
DOI: 10.1055/s-0032-1320395

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

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.