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

ID: ALA4811236

Journal: Bioorg Med Chem Lett

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

Authors: Yarovaya OI, Kovaleva KS, Zaykovskaya AA, Yashina LN, Scherbakova NS, Scherbakov DN, Borisevich SS, Zubkov FI, Antonova AS, Peshkov RY, Eltsov IV, Pyankov OV, Maksyutov RA, Salakhutdinov NF.

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.

CiteXplore: 33705902

DOI: 10.1016/j.bmcl.2021.127926

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