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

Bioorg Med Chem Lett. 2021 May 15:40:127926. doi: 10.1016/j.bmcl.2021.127926.

Olga I Yarovaya ¹, Kseniya S Kovaleva ¹, Anna A Zaykovskaya ², Liudmila N Yashina ², Nadezda S Scherbakova ², Dmitry N Scherbakov ², Sophia S Borisevich ³, Fedor I Zubkov ⁴, Alexandra S Antonova ⁴, Roman Yu Peshkov ⁵, Ilia V Eltsov ⁵, Oleg V Pyankov ², Rinat A Maksyutov ², Nariman F Salakhutdinov ¹

Affiliations

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

PMID: 33705902 DOI: 10.1016/j.bmcl.2021.127926

Abstract

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.

Keywords

Antiviral; HFRS; Hantavirus; Isoindole; Terpene.

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