New class of hantaan virus inhibitors based on conjugation of the isoindole fragment to (+)-camphor or (−)-fenchone hydrazonesv

New class of hantaan virus inhibitors based on conjugation of the isoindole fragment to (+)-camphor or (−)-fenchone hydrazonesv Научная публикация

Журнал

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Вых. Данные

Год: 2021, Том: 40, Номер статьи : 127926, Страниц : DOI: 10.1016/j.bmcl.2021.127926

Ключевые слова

Antiviral; Hantavirus; HFRS; Isoindole; Terpene

Авторы

Yarovaya O.I. ¹ , Kovaleva K.S. ¹ , Zaykovskaya A.A. ² , Yashina L.N. ² , Scherbakova N.S. ² , Scherbakov D.N. ² , Borisevich S.S. ³ , Zubkov F.I. ⁴ , Antonova A.S. ⁴ , Peshkov R.Y. ⁵ , Eltsov I.V. ⁵ , Pyankov O.V. ² , Maksyutov R.A. ² , Salakhutdinov N.F. ¹

Организации

1	N.N. Vorozhtsov, Novosibirsk Institute of Organic Chemistry SB RAS, Lavrent'ev av., 9, Novosibirsk, 630090, Russian Federation
2	State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, Novosibirsk Region 630559, Russian Federation
3	Ufa Institute of Chemistry, Ufa Federal Research Center, RAS, Octyabrya pr., 71, Ufa, 450054, Russian Federation
4	Organic Chemistry Department, Faculty of Science, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow, 117198, Russian Federation
5	Novosibirsk State University, Pirogova St. 1, Novosibirsk, 630090, Russian Federation

This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76–118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC50 = 7.6 ± 2 µM) along with low toxicity (CC50 > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established. © 2021 Elsevier Ltd

Yarovaya O.I. , Kovaleva K.S. , Zaykovskaya A.A. , Yashina L.N. , Scherbakova N.S. , Scherbakov D.N. , Borisevich S.S. , Zubkov F.I. , Antonova A.S. , Peshkov R.Y. , Eltsov I.V. , Pyankov O.V. , Maksyutov R.A. , Salakhutdinov N.F.
New class of hantaan virus inhibitors based on conjugation of the isoindole fragment to (+)-camphor or (−)-fenchone hydrazonesv
Bioorganic and Medicinal Chemistry Letters. 2021. V.40. 127926 . DOI: 10.1016/j.bmcl.2021.127926 WOS Scopus РИНЦ

Опубликована в печати:

1 мая 2021 г.

Web of science	WOS:000663617300011
Scopus	2-s2.0-85102584920
РИНЦ	46765538
OpenAlex	W3133578341