Synthesis of highly functionalized barbituric acids and study of their interactions with p-glycoprotein and Mg2+--potential candidates for multi drug resistance modulation

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.