title: Synthesis of highly functionalized barbituric acids and study of their interactions with p-glycoprotein and Mg2+--potential candidates for multi drug resistance modulation.
abstract: A number of barbituric acids with appropriate substituent at C-5 position were synthesized and investigated for their interactions with p-gp and Mg(2+). Compounds 5, 6, 8-10, 12-14 and 16 increased the basal activity of p-gp by more than 50% at 0.05 muM concentration. Molecular docking indicate a number of H-bond interactions between these molecules and the amino acid residues of ATP binding site of p-gp. These molecules also showed appreciable interactions with Mg(2+), an important component of efflux pump. All the results of these investigations favor the suitability of barbituric acids toward MDR modulation.
authors.affiliation: Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India. palwinder_singh_2000@yahoo.com
authors.forename: Palwinder
authors.initials: P
authors.lastname: Singh
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Atul
authors.initials: A
authors.lastname: Bhardwaj
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000378:metabolism; D001463:Barbiturates / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D020128:Inhibitory Concentration 50; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001463:Barbiturates; D008274:Magnesium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C032232:barbituric acid