Molecular docking and P-glycoprotein inhibitory activity of Flavonoids

Flavonoids are the most common group of phenolic compounds that have anti-carcinogenic properties and are the constituents of fruits, vegetables and plant derived beverages. In the present study, Flavonoids were docked to three-dimensional structure of P-glycoprotein which plays an important role in multi drug resistance. A three-dimensional homology model of human P-glycoprotein was built, based on the crystal structure of the 3G5U (Chain A; Structure of a bacterial multidrug ABC transporter) by using Modeller7v7 software. Homology modelling provided a good quality model of the corresponding region in human P-glycoprotein. With the aid of the molecular mechanics and molecular dynamics methods, the final model is obtained and is further assessed by PROCHECK and verify 3D graph programs, which showed that the final refined model is reliable. With this model, a flexible docking study of P-glycoprotein with a group of Flavonoids which were selected from the previous publications was performed. The results indicated THR37, ALA42, ARG40 and ARG47 in P-glycoprotein are important determinant residues in binding as they have strong hydrogen bonding with Flavonoids. These hydrogen binding interactions play an important role for stability of the complex. Among the 10 Flavonoids docked, BiochaninA showed best docking result with P-glycoprotein. Our results may be helpful for further experimental investigations.