Designing potent inhibitors against the multidrug resistance P-glycoprotein

The multidrug transporter P-glycoprotein is an ATP binding cassette (ABC) exporter responsible for resistance to tumor cells during chemotherapy. This study was designed with computational approaches aimed at identifying the best potent inhibitors of P-glycoprotein. Although many compounds have been suggested to inhibit P-glycoprotein, however, their information on bioavailability, selectivity, ADMET properties, and molecular interactions has not been revealed. Molecular docking, ADMET analysis, molecular dynamics, Principal component analysis (PCA), and binding free energy calculations were performed. Two compounds D1 and D2 showed the best docking score against P-glycoprotein and both compounds have 4-thiazolidinone derivatives containing indolin-3 one moiety are novel anti-tumor compounds. ADMET calculation analysis predicted D1 and D2 to have acceptable pharmacokinetic properties. The MD simulation discloses that D1-P-glycoprotein…