Modeling of Multidrug Resistance Protein of Leishmania Donovani and Insilico Prediction of Active Drugs

Leishmaniasis is a protozoal disease which afflicts the world’s poorest population with endemic distribution in 88 countries around the world and has been considered as a major tropical disease by the world health organization (WHO). P-glycoprotein (P-gp) is an ATP-dependent pump that exports a wide range of drugs from the cell, decreasing their intracellular concentration and preventing their cytotoxic activity. P-gp belongs to the ABC super family of transporters. A three dimensional structure of P-glycoprotein of Leishmania donovani was constructed through homology modeling using X-ray crystal structure of multi drug transporter protein sav1866 (pdb id: 2HYD) complex as template using Modeller 9v5. Virtual high throughput screening of one hundred fifty compounds (anthracyclines, alkaloids, xanthons, peptides and natural phenolic compounds) with the modeled P-glycoprotein (Pgp) for the potential P-glycoprotein inhibitors, using AutoDock4.0, GOLDv2.1 and Ligand Fit of discovery studio. Among all inhibitors, two compounds conivapton and nizatidine have shown highest ligand fit score while imatinib, telmisarton, dasatinib have shown better fitness score and formation of hydrogen bonds. These compounds may act as potential drug candidates against P-glycoprotein of Leishmania donovani.