Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

Scientia Pharmaceutica

Andrii Lozynskyi¹  Serhii Holota¹  Roman Lesyk¹  Mariia Mishchenko²  Sergiy Shtrygol’²  Volodymyr Novikov³  Semen Khomyak³  Olexandr Karpenko⁴ 

[1] Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska, 79010 Lviv, Ukraine;Department of Pharmacology and Pharmacotherapy, National University of Pharmacy, 53 Pushkinska, 61002 Kharkiv, Ukraine;Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University,12 Bandery, 79013 Lviv, Ukraine;Enamine Ltd., 23 Alexandra Matrosova, 01103 Kiev, Ukraine;

关键词: 4-thiazolidinones;    darbufelone;    dual COX-2/5-LOX inhibitor;    pentylenetetrazole seizure;    anticonvulsant activity;   

DOI  :  10.3390/scipharm89020022

来源: DOAJ

【 摘 要 】

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

【 授权许可】

Unknown