КФУ. Карточка публикации. Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile

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NOVEL POTENT PYRIDOXINE-BASED INHIBITORS OF ACHE AND BCHE, STRUCTURAL ANALOGS OF PYRIDOSTIGMINE, WITH IMPROVED IN VIVO SAFETY PROFILE

Форма представления

Статьи в российских журналах и сборниках

Год публикации

2016

Язык

английский

Авторы, сотрудники КФУ

Зобов Владимир Васильевич, автор

Никольский Евгений Евгеньевич, автор

Петров Константин Александрович, автор

Стрельник Алексей Дмитриевич, автор

Штырлин Юрий Григорьевич, автор

Библиографическое описание на языке оригинала

Strelnik A.D. Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile/ A.D. Strelnik, A.S. Petukhov, I.V. Zueva, V.V. Zobov, K.A. Petrov, E.E. Nikolsky, K.V. Balakin, S.O. Bachurin, Y.G. Shtyrlin //Bioorganic and Medicinal Chemistry Letters. - 2016. - Vol.26, Is.16. - P.4092-4094.

Аннотация

We report a novel class of carbamate-type ChE inhibitors, structural analogs of pyridostigmine. A small library of congeneric pyridoxine-based compounds was designed, synthesized and evaluated for AChE and BChE enzymes inhibition in vitro. The most active compounds have potent enzyme inhibiting activity with IC50 values in the range of 0.46?2.1 μM (for AChE) and 0.59?8.1 μM (for BChE), with moderate selectivity for AChE comparable with that of pyridostigmine and neostigmine. Acute toxicity studies using mice models demonstrated excellent safety profile of the obtained compounds with LD50 in the range of 22?326 mg/kg, while pyridostigmine and neostigmine are much more toxic (LD50 3.3 and 0.51 mg/kg, respectively). The obtained results pave the way to design of novel potent and safe cholinesterase inhibitors for symptomatic treatment of neuromuscular disorders.

Ключевые слова

Acetylcholinesterase (AChE) inhibitors; Carbamate cholinesterase inhibitors; Neuromuscular disorders treatment; Pyridostigmine analogs; Substituted pyridoxines

Название журнала

Bioorganic and Medicinal Chemistry Letters

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979536977&partnerID=40&md5=d2a90aa6e3f1e57c41abecb2cf65ccce

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https://repository.kpfu.ru/?p_id=136020

Полная запись метаданных

Поле DC	Значение	Язык
dc.contributor.author	Зобов Владимир Васильевич	ru_RU
dc.contributor.author	Никольский Евгений Евгеньевич	ru_RU
dc.contributor.author	Петров Константин Александрович	ru_RU
dc.contributor.author	Стрельник Алексей Дмитриевич	ru_RU
dc.contributor.author	Штырлин Юрий Григорьевич	ru_RU
dc.date.accessioned	2016-01-01T00:00:00Z	ru_RU
dc.date.available	2016-01-01T00:00:00Z	ru_RU
dc.date.issued	2016	ru_RU
dc.identifier.citation	Strelnik A.D. Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile/ A.D. Strelnik, A.S. Petukhov, I.V. Zueva, V.V. Zobov, K.A. Petrov, E.E. Nikolsky, K.V. Balakin, S.O. Bachurin, Y.G. Shtyrlin //Bioorganic and Medicinal Chemistry Letters. - 2016. - Vol.26, Is.16. - P.4092-4094.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/?p_id=136020	ru_RU
dc.description.abstract	Bioorganic and Medicinal Chemistry Letters	ru_RU
dc.description.abstract	We report a novel class of carbamate-type ChE inhibitors, structural analogs of pyridostigmine. A small library of congeneric pyridoxine-based compounds was designed, synthesized and evaluated for AChE and BChE enzymes inhibition in vitro. The most active compounds have potent enzyme inhibiting activity with IC50 values in the range of 0.46?2.1 μM (for AChE) and 0.59?8.1 μM (for BChE), with moderate selectivity for AChE comparable with that of pyridostigmine and neostigmine. Acute toxicity studies using mice models demonstrated excellent safety profile of the obtained compounds with LD50 in the range of 22?326 mg/kg, while pyridostigmine and neostigmine are much more toxic (LD50 3.3 and 0.51 mg/kg, respectively). The obtained results pave the way to design of novel potent and safe cholinesterase inhibitors for symptomatic treatment of neuromuscular disorders.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile	ru_RU
dc.type	Статьи в российских журналах и сборниках	ru_RU