Triblock Conjugates: Identification of a Highly Potent Antiinflammatory Agent

Rationally
designed conjugates of chrysin, indole, and barbituric acid were synthesized
and screened for their antiinflammatory activities through in vitro
and in vivo experiments. Improved over the previously reported chrysin–indole–pyrazole
conjugates and also in comparison to the chrysin, indole, and barbituric
acid based COX-2 inhibitors, the new compounds have displayed significantly
better IC50 for COX-2 and some of them also exhibited inhibition
of 5-LOX enzyme. For one of the test compounds, IC50 for
COX-2 and 5-LOX was 1 and 1.5 nM, respectively. Investigations of
Swiss Albino mice through capsaicin induced paw lickings and dextran
induced inflammation showed that these compounds possess appreciable
analgesic and antiinflammatory activities. Ki, Ka, and ΔG for the enzyme–compound interaction were calculated and found
to be in agreement with the biological data. The experimental results
were supported by the molecular docking studies of the compounds in
the active site of COX-2 and 5-LOX. Overall, a highly promising antiinflammatory
agent was identified.