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.
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Exploring the Role of Gene Therapy for Neurological Disorders
Current Gene Therapy Interaction of Steroids with the GABA-A Receptor
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Bringing Drugs Into the Injured Brain and Keeping Them There (Executive Guest Editors: Dirk M. Hermann and Pauline Patak)]
Current Pharmaceutical Design Medications not Intended for Treatment of Dyslipidemias and with a Variable Effect on Lipids
Current Pharmaceutical Design PET Radiotracers for Molecular Imaging of Serotonin 5-HT<sub>1A</sub> Receptors
Current Medicinal Chemistry Multiple Roles for Glycogen Synthase Kinase-3 as a Drug Target in Alzheimers Disease
Current Drug Targets Cardio-Hepatic Metabolic Derangements and Valproic Acid
Current Clinical Pharmacology Antimicrobial Activity of SPC13, New Antimicrobial Peptide Purified from Scolopendra polymorpha Venom
Anti-Infective Agents Recent Software Developments and Applications in Functional Imaging
Current Pharmaceutical Biotechnology A Synopsis of Nano-Technological Approaches Toward Anti-Epilepsy Therapy: Present and Future Research Implications
Current Drug Metabolism Recent Advances on Neural Tube Defects with Special Reference to Valproic Acid
Endocrine, Metabolic & Immune Disorders - Drug Targets Models in Research of Pharmacoresistant Epilepsy: Present and Future in Development of Antiepileptic Drugs
Current Medicinal Chemistry Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat
Current Pharmaceutical Design Adult Neurogenesis and the Diseased Brain
Current Medicinal Chemistry Gabapentin and Pregabalin for the Acute Post-operative Pain Management. A Systematic-narrative Review of the Recent Clinical Evidences
Current Drug Targets Standardization Using Analytical Techniques (UV, NMR, FTIR, HPLC, Mass) and Pharmacognostic Evaluation of the Roots of <i>Selinum vaginatum</i>: A Rare Himalayan Plant of the Rohtang Region
Current Biotechnology Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels
Current Neuropharmacology The Role of IRE1 Signaling in the Central Nervous System Diseases
Current Neuropharmacology White Matter Damage Along the Uncinate Fasciculus Contributes to Cognitive Decline in AD and DLB
Current Alzheimer Research Commentary (Research Highlights: Transcranial Drug Delivery for Neurological Disorders)
CNS & Neurological Disorders - Drug Targets