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Discovery of Benzenesulfonamide Derivatives as Carbonic Anhydrase Inhibitors with Effective Anticonvulsant Action: Design, Synthesis, and Pharmacological Evaluation. 2018

Chandra Bhushan Mishra, and Shikha Kumari, and Andrea Angeli, and Silvia Bua, and Manisha Tiwari, and Claudiu T Supuran
Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Center for Biomedical Research , University of Delhi , 110007 Delhi , India.

Two series of novel benzenesulfonamide derivatives were synthesized and evaluated for their human carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against four isoforms, hCA I, hCA II, hCA VII, and hCA IX. It was found that compounds of both series showed low to medium nanomolar inhibitory potential against all isoforms. Some of these derivatives displayed selective inhibition against the epileptogenesis related isoforms hCA II and VII, within the nanomolar range. These potent hCA II and VII inhibitors were evaluated as anticonvulsant agents against MES and sc-PTZ induced convulsions. These sulfonamides effectively abolished induced seizures in both models. Furthermore, time dependent seizure protection capability of the most potent compound was also evaluated. A long duration of action was displayed, with efficacy up to 6 h after drug administration. The compound appeared as an orally active anticonvulsant agent without showing neurotoxicity in a rotarod test, a nontoxic chemical profile being observed in subacute toxicity study.

UI MeSH Term Description Entries
D008297 Male Males
D010433 Pentylenetetrazole A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D002257 Carbonic Anhydrase Inhibitors A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES. Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D003292 Convulsants Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. Convulsant,Convulsant Effect,Convulsant Effects,Effect, Convulsant,Effects, Convulsant
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D004856 Postural Balance A POSTURE in which an ideal body mass distribution is achieved. Postural balance provides the body carriage stability and conditions for normal functions in stationary position or in movement, such as sitting, standing, or walking. Postural Control,Posture Balance,Posture Control,Posture Equilibrium,Balance, Postural,Musculoskeletal Equilibrium,Postural Equilibrium,Balance, Posture,Control, Postural,Control, Posture,Equilibrium, Musculoskeletal,Equilibrium, Postural,Equilibrium, Posture,Postural Controls,Posture Balances,Posture Controls,Posture Equilibriums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic

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