Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators

P-glycoprotein (Pgp), an ATP binding cassette (ABC) trans-porter, is an ATP-dependent efflux pump responsible for cancer multidrugresistance. As part of efforts to identify human Pgp (hPgp) inhibitors, weprepared a series of novel triazole-conjugated dihydropyrimidinones using asynthetic approach that is well suited for obtaining compound libraries. Several ofthese dihydropyrimidinone derivatives modulate human P-glycoprotein (hPgp)activity with low micromolar EC50values. Molecular docking studies suggest thatthese compounds bind to the M-site of the transporter