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Novel Dihydropyrimidinone Derivatives as Potential P-Glycoprotein Modulators
Sabera Bijani1,2, Faraz Shaikh1,3, Sheefa Mirza4,5
1Center of Excellence, National Facility for Drug Discovery Complex, Department of Chemistry, Saurashtra University, Rajkot 360005, India.
Abstract:
P-glycoprotein (Pgp), an ATP binding cassette (ABC) transporter, is an ATP-dependent efflux pump responsible for cancer multidrug resistance. As part of efforts to identify human Pgp (hPgp) inhibitors, we prepared a series of novel triazole-conjugated dihydropyrimidinones using a synthetic approach that is well suited for obtaining compound libraries. Several of these dihydropyrimidinone derivatives modulate human P-glycoprotein (hPgp) activity with low micromolar EC50 values. Molecular docking studies suggest that these compounds bind to the M-site of the transporter.
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