Abstract
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.
Central Nervous System Agents in Medicinal Chemistry
Title:In Silico Validation and Structure Activity Relationship Study of a Series of Pyridine-3-carbohydrazide Derivatives as Potential Anticonvulsants in Generalized and Partial Seizures
Volume: 13 Issue: 2
Author(s): Reema Sinha, Udai Vir Singh Sara, Ratan Lal Khosa, James Stables and Jainendra Jain
Affiliation:
Keywords: Anticonvulsant, 2A1H, corneal kindling, 6Hz, MES, 1OHV, 1PBQ, scPTZ.
Abstract: 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.
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Sinha Reema, Sara Vir Singh Udai, Khosa Lal Ratan, Stables James and Jain Jainendra, In Silico Validation and Structure Activity Relationship Study of a Series of Pyridine-3-carbohydrazide Derivatives as Potential Anticonvulsants in Generalized and Partial Seizures, Central Nervous System Agents in Medicinal Chemistry 2013; 13 (2) . https://dx.doi.org/10.2174/1871524911313020006
DOI https://dx.doi.org/10.2174/1871524911313020006 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
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