Design, Synthesis, Anti-inflammatory & Anticonvulsant Activity of Substituted Heterocyclic Compounds

Aim: To design, synthesize, anti-inflammatory & anticonvulsant activity of substituted coumarin acetohydrazide derivatives.

Study Design: Experimental work related to Anti-inflammatory & Anticonvulsant activity.

Methodology: Coumarin acetohydrazide derivatives were synthesized by reacting substituted isatin with 7-hydroxy-4-methyl-coumarin in glacial acetic acid to determine their anti-inflammatory & anticonvulsant activities. Molecular docking study was performed against the COX enzyme for anti-inflammatory activity & carbonic anhydrase II enzyme for anticonvulsant activity. Anti-inflammatory activity was done by carrageenan induced paw edema method in rats at a dose of 200 mg/kg body weight. Anticonvulsant activity was studied in rats at a dose of 200 mg/kg body weight; in the maximal electroshock (MES) induced seizures model.

Results: (Z)-2-(4,8-dimethyl-2-oxo-2H-chromen-7-yl)oxy)-N-(5-nitro-2-oxoindolin-3-ylidine) aceto-hydrazide and (Z)-2-(4-methyl-2-oxo-2H-chromen-7yl) oxy)-N-(1-methyl-2-oxoindolin-3-ylidene) acetohydrazide showed the highest anti-inflammatory activity as compared to Celecoxib after 5 h with 71.94 to 77.96 % inhibition. Most of the compounds displayed anticonvulsant activity in the MES screen at a dose 200 mg/kg. Out of twelve compounds (Z)-N-(5-chloro-2-oxoindolin-3-ylidene)-2-((4-methyl-2-oxo-2H-chromen-7-yl) oxy) acetohydrazide and (Z)-2-((4-methyl-2-oxo-2H-chromen-7yl) oxy)-N-(1-methyl-2-oxoindolin-3-ylidene) acetohydrazide shown most significant activity with remarkable protection (67%) against MES induced convulsions. The structure-activity relationship concluded valuable pharmacophoric information, that the substitution on isatin ring has a significant effect on preventing inflammation & the seizure formation.

Conclusion: From the molecular docking study & biological activity determines that all synthesized coumarin acetohydrazide derivatives shows anti-inflammatory activity as compared to Celecoxib & anticonvulsant activity as compared to Phenytoin.