A series of 3, 6 di substituted-7-hydroxy-2-methyl-4H-1-benzopyran-4-one derivatives (Chromone Biheterocycles)
were synthesized and their structures were established on the basis of modern analytical techniques (1HNMR, 13CNMR and
HRMS). All the synthesized compounds were tested for their in vitro anti-inflammatory activity. Among the 21 Synthesized
derivatives, Pyrazole linked benzopyran-4-one derivative Compound 7s (IC50= 23.14), Imidazole linked benzopyran-4-one
derivatives Compounds 7g (IC 50= 17.52) and 7k (IC50= 19.68) have significant anti-inflammatory activity in comparison with
the Diclofenac as control standard (IC50= 16.23). Further demonstrated the mechanism of anti-inflammatory activity for the
compounds 7g (2 IC50= 13.5) and 7k (2 IC50= 17.1) using TNF-α ELISA based assay in comparison with the Infliximab (IC50=
12.9) as control standard. Animal experiments were carried out to find the in-vivo efficacy of compound 7g through carrageenaninduced rat paw edema assay method. The results demonstrated that Compound (7g) had significant anti‐inflammatory activity at
doses of 50 and 75 mg/kg, had the best significant reduction and inhibition of edema with 82.28, 88.61% and 84.34, 91.57% at
third hour and fourth hour respectively, and similar as compared with standard drug Diclofenac 50 mg/kg body weight (p < 0.05).
Molecular docking interactions of Compound 7g with TNF-α (2AZ5) using glide protocol of Schrodinger suite revealed best
possible pose with a dock score of 9.6. Altogether, our findings suggest that Compound 7g is a promising anti-inflammatory
drug candidate, in the management of inflammation and pain conditions.
Key words: Chromones, Imidazole, Pyrazole, Anti-inflamatory activity.
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