Design and synthesis of some coumarin derivatives with potential central nervous system activity / Mostafa Abdelmohsen Anwar Taha ; Supervised Samir Mohamed Elmnoghazy , Essam Eldin A. Osman , Walaa Hamada Abdallah

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

Anticonvulsants are also being used in the treatment of neuropathic pain and as mood stabilizers in the treatment of psychiatric disorders such as bipolar disorder.Coumarin derivatives have reported potent anticonvulsant activities with the multi-target mechanism. Hence, they represent an attractive scaffold for designing new safe compound with anticonvulsant activity.Thus, were synthesized in this investigation, twenty new 8-allyl substituted and 8-Allyl-7-acetoxyhydrazide-4-methylcoumarin derivative was considered a key intermediate for the preparation a wide range of cyclic imide (VI), dimethyl Pyrazole (VII), oxopyrazole (VIII), thiosemicarbazones (Xa,b-XIIIa,b), 4-substituted benzylidene (XIVa-h) and semicarbazone (XVI) substituents. All the prepared compounds were evaluated for their anticonvulsant activity where three compounds VI, VII and Xb exhibited 100% protection in scPTZ screening at a dose of 100 mg/kg relative to phenobarbital 100% protection (30 mg/kg) and ethosuximide 100% protection (150 mg/kg), the most active compounds were subjected to quantification study for determination their ED50. A molecular docking study was performed To rationalize the anticonvulsant activity of the prepared compounds, they were docked into GABA-AT crystal structure (PDB: 1OHW)

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