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 Mg2+. Compounds 5, 6, 8–10, 12–14 and 16 increased the basal activity of p-gp by more than 50% at 0.05 μM 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 Mg2+, an important component of efflux pump. All the results of these investigations favor the suitability of barbituric acids toward MDR modulation.

Graphical abstractBarbituric acid derivatives exhibit significant interactions with p-gp and Mg2+ and could be useful for MDR modulation.Figure optionsDownload full-size imageDownload as PowerPoint slide