ISSN: 1875-6166 (Online)
ISSN: 1871-5249 (Print)

Volume 14, 2 Issues, 2014

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Central Nervous System Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Gregory. S. Hamilton
Intellectual Property Dept. Eisai Inc.
6611 Tributary Street
Baltimore, MD 21224

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In Silico Validation and Structure Activity Relationship Study of a Series of Pyridine-3-carbohydrazide Derivatives as Potential Anticonvulsants in Generalized and Partial Seizures

Author(s): Reema Sinha, Udai Vir Singh Sara, Ratan Lal Khosa, James Stables and Jainendra Jain

Affiliation: Department of Pharmacy, RamEesh Institute of Vocational and Technical Education, 3, Knowledge Park I, Greater Noida, Gautam Budh Nagar, Uttar Pradesh, India-201310.


A series of twelve compounds (Compounds RNH1–RNH12) of acid hydrazones of pyridine-3-carbohydrazide or nicotinic acid hydrazide was synthesized and evaluated for anticonvulsant activity by MES, scPTZ, minimal clonic seizure and corneal kindling seizure test. Neurotoxicity was also determined for these compounds by rotarod test. Results showed that halogen substitution at meta and para position of phenyl ring exhibited better protection than ortho substitution. Compounds RNH4 and RNH12, were found to be the active analogs displaying 6Hz ED50 of 75.4 and 14.77 mg/kg while the corresponding MES ED50 values were 113.4 and 29.3 mg/kg respectively. In addition, compound RNH12 also showed scPTZ ED50 of 54.2 mg/kg. In the series, compound RNH12 with trifluoromethoxy substituted phenyl ring was the most potent analog exhibiting protection in all four animal models of epilepsy. Molecular docking study has also shown significant binding interactions of these two compounds with 1OHV, 2A1H and 1PBQ receptors. Thus, N-[(meta or para halogen substituted) benzylidene] pyridine-3-carbohydrazides could be used as lead compounds in anticonvulsant drug design and discovery.

Keywords: Anticonvulsant, 2A1H, corneal kindling, 6Hz, MES, 1OHV, 1PBQ, scPTZ.

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Article Details

Volume: 13
Issue Number: 2
First Page: 132
Last Page: 140
Page Count: 9
DOI: 10.2174/1871524911313020006

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