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

被引：5
|
作者：
Mishchenko, Mariia [1 ]
Shtrygol', Sergiy [1 ]
Lozynskyi, Andrii [2 ]
Khomyak, Semen [3 ]
Novikov, Volodymyr [3 ]
Karpenko, Olexandr [4 ]
Holota, Serhii [2 ,5 ]
Lesyk, Roman [2 ,6 ]
机构：
[1] Natl Univ Pharm, Dept Pharmacol & Pharmacotherapy, 53 Pushkinska, UA-61002 Kharkiv, Ukraine
[2] Danylo Halytsky Lviv Natl Med Univ, Dept Pharmaceut Organ & Bioorgan Chem, 69 Pekarska, UA-79010 Lvov, Ukraine
[3] Lviv Polytech Natl Univ, Dept Technol Biol Act Subst Pharm & Biotechnol, 12 Bandery, UA-79013 Lvov, Ukraine
[4] Enamine Ltd, 23 Alexandra Matrosova, UA-01103 Kiev, Ukraine
[5] Lesya Ukrainka Volyn Natl Univ, Dept Organ Chem & Pharm, Volya Ave 13, UA-43025 Lutsk, Ukraine
[6] Univ Informat Technol & Management Rzeszow, Dept Publ Hlth Dietet & Lifestyle Disorders, Fac Med, Sucharskiego 2, PL-35225 Rzeszow, Poland
来源：
SCIENTIA PHARMACEUTICA | 2021年 / 89卷 / 02期
基金：
新加坡国家研究基金会;
关键词：
4-thiazolidinones; darbufelone; dual COX-2; 5-LOX inhibitor; pentylenetetrazole seizure; anticonvulsant activity; NEUROINFLAMMATION; EPILEPSY; CHALLENGES; RATS; MICE;
D O I：
10.3390/scipharm89020022
中图分类号：
R9 [药学];
学科分类号：
1007 ;
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.
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页数：10
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