(+)-Fenchol and (-)-Isopinocampheol Derivatives Targeting the Entry Process of Filoviruses | Sciact - CRIS-система Института катализа

(+)-Fenchol and (-)-Isopinocampheol Derivatives Targeting the Entry Process of Filoviruses Научная публикация

Журнал

European Journal of Medicinal Chemistry
ISSN: 0223-5234 , E-ISSN: 1768-3254

Вых. Данные

Год: 2024, Том: 275, Номер статьи : 116596, Страниц : 16 DOI: 10.1016/j.ejmech.2024.116596

Ключевые слова

Fenchol; Isopinocampheol; Ebola virus; Marburg virus; Glycoprotein; Lysosomotropic compounds

Авторы

Sokolova Anastasiya S. ¹ , Baev Dmitriy S. ^1,2 , Mordvinova Ekaterina D. ³ , Yarovaya Olga I. ¹ , Volkova Natalia V. ³ , Shcherbakov Dmitriy N. ³ , Okhina Alina A. ¹ , Rogachev Artem D. ¹ , Shnaider Tatiana A. ⁴ , Chvileva Anastasiya S. ⁵ , Nikitina Tatiana V. ⁶ , Tolstikova Tatyana G. ¹ , Salakhutdinov Nariman F. ¹

Организации

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russian Federation
2	SRF SKIF, Koltsovo, Novosibirsk Oblast, 630559, Russian Federation
3	State Research Center of Virology and Biotechnology VECTOR (Rospotrebnadzor), Koltsovo, Novosibirsk Oblast, 630559, Russian Federation
4	Institute of Cytology and Genetics (ICG), SB RAS, Novosibirsk, 630090, Russian Federation
5	Novosibirsk State University, Novosibirsk, 630090, Russian Federation
6	Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050, Russian Federation

Информация о финансировании (2)

1	Министерство науки и высшего образования Российской Федерации (с 15 мая 2018)	FWUR-2024-0040
2	Российский научный фонд	22-73-00168

The increasing frequency of filovirus outbreaks in African countries has led to a pressing need for the development of effective antifilovirus agents. In continuation of our previous research on the antifilovirus activity of monoterpenoid derivatives, we synthesized a series of (+)-fenchol and (−)-isopinocampheol derivatives by varying the type of heterocycle and linker length. Derivatives with an N-alkylpiperazine cycle proved to be the most potent antiviral compounds, with half-maximal inhibitory concentration (IC50) 1.4–20 μМ against Lenti-EboV-GP infection and 11.3–47 μМ against Lenti-MarV-GP infection. Mechanism-of-action experiments revealed that the compounds may exert their action by binding to surface glycoproteins (GPs). It was demonstrated that the binding of the synthesized compounds to the Marburg virus GP is less efficient as compared to the Ebola virus GP. Furthermore, it was shown that the compounds possess lysosomotropic properties. Thus, the antiviral activity may be due to dual effects. This study offers new antiviral agents that are worthy of further exploration.

Sokolova A.S. , Baev D.S. , Mordvinova E.D. , Yarovaya O.I. , Volkova N.V. , Shcherbakov D.N. , Okhina A.A. , Rogachev A.D. , Shnaider T.A. , Chvileva A.S. , Nikitina T.V. , Tolstikova T.G. , Salakhutdinov N.F.
(+)-Fenchol and (-)-Isopinocampheol Derivatives Targeting the Entry Process of Filoviruses
European Journal of Medicinal Chemistry. 2024. V.275. 116596 :1-16. DOI: 10.1016/j.ejmech.2024.116596 WOS Scopus CAPlus PMID OpenAlex СКИФ ID

Поступила в редакцию:	27 апр. 2024 г.
Принята к публикации:	11 июн. 2024 г.
Опубликована online:	15 июн. 2024 г.
Опубликована в печати:	5 сент. 2024 г.

Web of science:	WOS:001257244000001
Scopus:	2-s2.0-85196192293
Chemical Abstracts:	2024:1388533
PMID (PubMed):	38889610
OpenAlex:	W4399696820
СКИФ ID:	3441

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