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

Authors :
Dmitry N. Scherbakov
Sophia S. Borisevich
Fedor I. Zubkov
Liudmila N. Yashina
Nariman F. Salakhutdinov
Olga I. Yarovaya
Roman Yu. Peshkov
Oleg V. Pyankov
Rinat A. Maksyutov
Alexandra S. Antonova
Nadezda S. Scherbakova
Ilia V. Eltsov
Anna A. Zaykovskaya
Kseniya S. Kovaleva
Source :
Bioorganicmedicinal chemistry letters. 40
Publication Year :
2020

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.

Details

ISSN :
14643405
Volume :
40
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry letters
Accession number :
edsair.doi.dedup.....5da4e7aecb709e0cd64c4597c1a1963b