Reversal of Multi-Drug Resistance: In-Silico Screening of P-glycoprotein inhibitors among Coumarin derivatives

Chemotherapeutic strategies often fail as a result of developing multi-drug resistance in malignant cells. Up-regulating ATP binding cassette efflux transporter proteins are responsible for such conditions in which the anticancer drugs are effectively pumped out of the cells. Among the transporters P-glycoprotein (P-gp) is the main target in drug discovery projects that aim reversal of multi-drug resistance. Here we screened the natural polyphenolic coumarin, and its known derivatives available from Pubchem for potent interactive compounds with P-gp. An in silico screening study was performed through modelling interactions by Autodock 4. Here we report two of the most potential compounds; 3-(2-phenoxy phenyl)acrylic acid followed by propyl coumarin-3- carboxylate; propyl-2-oxochromen-3-carboxylate. Both derivatives showed considerably low binding energy (≤ -8 kcal/mol) and inhibition constant in nanomolar concentrations. In conclusion coumarin derivatives may provide valuable candidates for further analysis in anti-cancer drug discovery

Keywords:

Drug discovery , P-glycoprotein , Multi-drug resistance , Coumarin derivatives