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Multi-Drug Resistance (MDR) exerted by tumor cells is majorly due to the overexpression of ATP Binding cassette transporters such as ABCB1/P-glycoprotein (P-gp). Annonaceous acetogenins (AGEs) exert anticancer activity by strongly inhibiting NADH oxidase of cancer cells. The present  in silico  study aims at screening a potent MDR inhibitor among acetogenins from the plant  Annona muricata . Twenty-four AGEs were selected and screened for their pharmacokinetic properties. An inward facing conformation of P-gp is required for understanding the interaction of AGEs at the drug binding region and hence the human P-gp protein was modeled. The selected compounds were then docked with the ATP binding site and the drug binding site of modeled human P-gp. Annonacin A.1, Annohexocin.1 and Annomuricin E.1 docked better with high MM/GBSA dG binding in the drug binding region as compared with the conventional drugs. These compounds had a better docking score as compared with control inhibitor drugs at the ATP binding region. The complexes were subjected to MD simulation and Annonacin A was stable throughout the simulation period. Therefore, Annonacin A might act as a competitive inhibitor for the chemo drugs for binding at the drug binding region of P-gp. Hence it is capable of decreasing the efflux of chemo drugs out of the cells by P-Glycoprotein/ABCB1/MDR1. With this computational study, it is concluded that this compound might potentially reverse MDR, and hence can be taken forward for validation studies. Communicated by Ramaswamy H. Sarma

Study on reversal of ABCB1 mediated multidrug resistance in Colon cancer by acetogenins: An in - silico approach