Binding of Modulators to the Mouse and Human Multidrug Resistance (MDR) P-glycoprotein. A Computational Study

GABRIEL. E. JARA, D. MARIANO A. VERA, ADRIANA B. PIERINI

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2013 vol. 46 p. 10 - 10

he human multidrug resistance (MDR) P-glycoprotein (P-gp) mediates the extrusion of chemotherapeutic drugs from cancer cells. Modulators are relevant pharmaceutical targets since they are intended to control or to inhibit its pumping activity. In the present work, a common binding site for Rhodamine 123 and modulators with different modulation activity was found by molecular docking over the crystal structure of the mouse P-gp. The modulators involved a family of compounds, including derivatives of the propiophenone (3-phenylpropiophenone nucleus) and XR9576 (tariquidar). Our results showed that the relative binding energies estimated by molecular docking were in good correlation with the experimental activities. Preliminary classical molecular dynamics results on selected P-gp/modulator complexes were also performed in order to understand the nature of the prevalent molecular interactions and the possible main molecular features that characterize a modulator. Besides, the results obt