Dithymoquinone as a novel inhibitor for 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) to prevent renal failure

TL;DR

This study identifies dithymoquinone (DTQ) from black cumin seed as a potential inhibitor of CMPF, a uremic toxin, by demonstrating its higher binding affinity to human serum albumin through molecular docking, suggesting therapeutic potential for renal failure.

Contribution

The paper introduces dithymoquinone as a novel inhibitor of CMPF, with detailed molecular docking analysis and ADME predictions supporting its therapeutic potential.

Findings

DTQ has higher binding affinity to HSA than CMPF.

DTQ exhibits favorable ADME properties for drug development.

Molecular docking shows strong interactions between DTQ and HSA.

Abstract

3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a major endogenous ligand found in the human serum albumin (HSA) of renal failure patients. It gets accumulated in the HSA and its concentration in sera of patients may reflect the chronicity of renal failure [1-4]. It is considered uremic toxin due to its damaging effect on the renal cells. The high concentrations of CMPF inhibit the binding of other ligands to HSA. Removal of CMPF is difficult through conventional hemodialysis due to its strong binding affinity. We hypothesized that the competitive inhibition may be helpful in removal of CMPF binding to HSA. A compound with higher HSA binding affinity than CMPF could be useful to prevent CMPF from binding so that CMPF could be excreted by the body through the urine. We studied an active compound dihydrothymoquinone/ dithymoquinone (DTQ) found in black cumin seed (Nigella sativa), which has higher binding affinity for HSA. Molecular docking simulations were performed to find the binding affinity of CMPF and DTQ with HSA. DTQ was found to have higher binding affinity possessing more interactions with the binding residues than the CMPF. We studied the binding pocket flexibility of CMPF and DTQ to analyze the binding abilities of both the compounds. We have also predicted the ADME properties for DTQ which shows higher lipophilicity, higher gastrointestinal (GI) absorption, and blood-brain barrier (BBB) permeability. We discovered that DTQ has potential to act as an inhibitor of CMPF and can be considered as a candidate for the formation of the therapeutic drug against CMPF.