  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.
