Abstract
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.
Highlights
Coumarin, a member of benzopyrone system either isolated from natural source like plant or synthesized chemically in the laboratory
In the present work coumarin derivatives molecular studies performed against target molecules like COX-1 enzyme for anti-inflammatory activity (PDB: 3PGH) &carbonic anhydrase II enzyme for anticonvulsant activity TE1 (PDB: 3F8E)
All computational work done on Pentium (R) Dual-Core CPUE5500@ 2.80 HGz with memory (RAM) =2.00 GB and docking was done by using V Life software.3D ultra 8.0 software was used to construct 3D structures of all compounds and optimized geometry of compounds by energy minimization with Merck Molecular Force Field (MMFF), Convergence criteria, systemic method (1000Kcal/mol) was selected for conformation generation and save generate conformer as a MDL Mol Files (*mol).For anti-inflammatory activity & Anticonvulsant activity two different target enzymes were selected
Summary
A member of benzopyrone system either isolated from natural source like plant or synthesized chemically in the laboratory. Current therapy to treat inflammation is use of steroidal & nonsteroidal drugs [14] The use of these antiinflammatory drugs is reported to cause some adverse effects like throat swelling, heartburn, indigestion, stomach ulcer, dizziness, allergic reactions like rashes etc. Drugs like levetiracetam (Keppra), lamotrigine (Lamictal), topiramate (Topamax), valproic acid (Depakote), carbamazepine (Tegretol), ethosuximide (Zarontin) available in market [19] These drugs may cause side effects like skin rashes, poor coordination, tiredness, fatigue, dizziness, short memory, confusion etc [20]. These undesirable side effects necessities need of development of new anticonvulsant derivatives [21]. In the present work coumarin derivatives molecular studies performed against target molecules like COX-1 enzyme for anti-inflammatory activity (PDB: 3PGH) &carbonic anhydrase II enzyme for anticonvulsant activity TE1 (PDB: 3F8E)
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