KFU. Card publication. 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

Form of presentation

Articles in Russian journals and collections

Year of publication

2016

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Authors, employees of KFU

Zobov Vladimir Vasilevich, author

Nikolskiy Evgeniy Evgenevich, author

Petrov Konstantin Aleksandrovich, author

Strelnik Aleksey Dmitrievich, author

Shtyrlin Yuriy Grigorevich, author

Bibliographic description in the original language

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.

Annotation

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.

Keywords

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

The name of the journal

Bioorganic and Medicinal Chemistry Letters

URL

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

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=136020&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Zobov Vladimir Vasilevich	ru_RU
dc.contributor.author	Nikolskiy Evgeniy Evgenevich	ru_RU
dc.contributor.author	Petrov Konstantin Aleksandrovich	ru_RU
dc.contributor.author	Strelnik Aleksey Dmitrievich	ru_RU
dc.contributor.author	Shtyrlin Yuriy Grigorevich	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/eng/?p_id=136020&p_lang=2	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	Articles in Russian journals and collections	ru_RU