Synthesis and Antiviral Activity of 21β-Acetyl-20β,28-Epoxy-18α,19βH-Ursane Derivatives Against Influenza H1N1 and SARS-Cov-2 Spike Pseudovirus

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发表日期：

2024年3月26日

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E. F. Khusnutdinova,
Z. I. Galimova,
A. V. Petrova,
E. V. Tretyakova,
I. E. Smirnova,
A. V. Slita,
S. V. Fedij,
V. V. Zarubaev,
S. Xiao,
X. Ma,
D. Zhou,
T. V. Rybalova,
D. N. Polovyanenko,
O. B. Kazakova

摘要

Allobetulin derivatives with rearranged E-ring exhibit important pharmacological properties against various viral pathogens. Basing on 3β-acetoxy-21β-acetyl-20β,28-epoxy-18α,19βH-ursane triterpenoid, obtained from allobetulin in one stage, a series of new derivatives have been synthesized and their antiviral activity against both influenza virus A (H1N1) and SARS-CoV-2 pseudovirus was evaluated. Among them, 2,3-indolo-allobetulone N-propargyl derivatives were the most efficacious against influenza virus with low toxicity (CC₅₀ × 300 μM) and IC₅₀ values of 7.04 to 3.5 μM and high selectivity indexes (SI 43 and 86). Compared with amodiaquine, a derivative with 3-pyridinylidene fragment 12 showed a weak antiviral activity against SARS-CoV-2 pseudovirus with an inhibition rate of 57.3% at a concentration of 20 μM. Further optimization to increase the cellular antiviral activity seems to be necessary to develop this series of triterpenoids as antiviral agents.