Graph Theoretical analysis and in silico modeling and molecular dynamic studies of fused indolin-2-one derivatives for the treatment of inflammation

Abstract In the present work, novel 3-(4-(5-(substituted phenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbonyl)phenylimino)-1-(substitutedmethyl)indolin-2-one derivatives were obtained via the reaction of 4-(1-(substituted methyl)-2-oxoindolin-3-ylideneamino) benzohydrazide with appropriate aromatic chalcone. The synthesized compounds were investigated for their in silico chemokine/CXCR6 inhibitory activity. The most effective chemokine inhibitors were also evaluated for their in vivo antiinflammatory activity. The 3-(4-(5-(4-Chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbonyl) phenylimino)-1-(morpholino methyl) indolin-2-one (5a) derivative showed significant chemokine inhibition with eleven amino acid interaction as compared with standard Acetaminophen whereas Celecoxib, Diclofenac, Indomethacin, Naproxen, Ibuprofen, Aspirin showed less amino acid interaction. Based on the theoretical study reports the in vivo antiinflammatory activity was performed for the 3-(4-(5-(substituted phenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbonyl)phenylimino)-1-(substitutedmethyl)indolin-2-one (5a-5l). The observed results of in vivo study indicate that the compounds 5a, 5c exhibited significant antiinflammatory activity.