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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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Research Article

Evaluation of Anticonvulsant Activity and Toxicity Screening of Semicarbazones Derived from Quinazolinone Scaffold

Author(s): Meena K. Yadav, Laxmi Tripathi* and Diptendu Goswami

Volume 15, Issue 5, 2019

Page: [573 - 581] Pages: 9

DOI: 10.2174/1573407214666180710143557

Price: $65

Abstract

Background: Epilepsy is one of the most prevalent noncommunicable neurological conditions. More than 10 million people in India are afflicted with epilepsy. Treatment available has many detrimental side effects. Up to one-third of epilepsy patients remain resistance to optimum drug treatment. These facts triggered the further scope and search for newer more effective and less toxic anticonvulsants.

Methods: Quinazolinone semicarbazone derivatives showing protection in chemoconvulsant induced seizure models (as reported in our previous study) were further screened in MES and scPTZ induced seizure models. Neurotoxicity was determined; quantification of anticonvulsant activity and toxicity was also done. Finally compounds were screened by liver functional test to ascertain the possible hepatotoxicity in the active compounds.

Results: Compounds N-1- (menthone) -N- {[3-(4-(substituted)-phenyl) -4-oxo- 3,4-dihydroquinazolin- 2-yl] methyl} semicarbazone (3A-d-4, 3B-d-4 and 3C-d-4) showed significant protection in both MES and scPTZ induced seizure model with no neurotoxicity at the given dose. In MES test, compounds showed an ED50 close to that of phenytoin and carbamazepine. They also showed Protective Index (PI) higher as compared to phenytoin and carbamazepine. A high safety profile (HD50/ED50 values) was noted and hypnosis, analgesia, and anesthesia were only observed at higher doses.

Conclusion: Compounds showed no significant increase or decrease in the concentration of alkaline phosphatase, Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), albumin and bilirubin.

Keywords: Quinazolinone semicarbazones, anticonvulsant activity, quantitative anticonvulsant evaluation, neurotoxicity, hepatotoxicity, epilepsy.

Graphical Abstract

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