Bijani Sabera, Shaikh Faraz, Mirza Sheefa, Weng In Siu Shirley, Jain Nayan, Rawal Rakesh, Richards Nigel G J, Shah Anamik, Radadiya Ashish
Center of Excellence, National Facility for Drug Discovery Complex, Department of Chemistry, Saurashtra University, Rajkot 360005, India.
Department of Chemistry, Marwadi University, Rajkot 360003, India.
ACS Omega. 2022 May 2;7(19):16278-16287. doi: 10.1021/acsomega.1c05839. eCollection 2022 May 17.
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 EC values. Molecular docking studies suggest that these compounds bind to the M-site of the transporter.
P-糖蛋白（Pgp）是一种ATP结合盒（ABC）转运蛋白，是一种依赖ATP的外排泵，与癌症多药耐药性有关。作为鉴定人P-糖蛋白（hPgp）抑制剂工作的一部分，我们采用了一种非常适合获取化合物库的合成方法，制备了一系列新型的三唑共轭二氢嘧啶酮。这些二氢嘧啶酮衍生物中有几种以低微摩尔EC值调节人P-糖蛋白（hPgp）的活性。分子对接研究表明，这些化合物与转运蛋白的M位点结合。
