tetano
Editor, Senior Moderator
Mol Pharm
. 2020 May 19.
doi: 10.1021/acs.molpharmaceut.0c00244. Online ahead of print.
Synthesis of a Hexavalent Betulinic Acid Derivative as a Hemagglutinin-Targeted Influenza Virus Entry Inhibitor
Yingying Chen, Xinchen Wang, Yinbiao Zhu, Longlong Si, Bo Zhang, Yongmin Zhang, Lihe Zhang, Demin Zhou, Sulong Xiao
Abstract
Naturally occurring pentacyclic triterpenes, such as betulinic acid and its derivatives, exhibit various pharmaceutical activities and have been the subject of great interest, in particular for their antiviral properties. Here, we found a new anti-influenza virus conjugate, hexakis 6-deoxy-6-[4-N-(3β-hydroxy-lup-20(29)-en-28-oate)aminomethyl-1H-1,2,3-triazol-1-yl]-2,3-di-O-acetyl-α-cyclodextrin (CYY1-11, 1), in a minilibrary of pentacyclic triterpene-cyclodextrin conjugates by performing a cell-based screening assay and then exploring the underlying mechanisms. Our results showed that conjugate 1 possessed a high level activity against influenza virus A/WSN/33, with an IC50 value of 5.20 ?M (SI > 38.4). Study of the mechanism of action indicated that conjugate 1 inhibited viral replication by directly targeting the influenza hemagglutinin protein (KD = 1.50 ?M), thus efficiently preventing the attachment of the virion to its receptors on host cells and subsequent infection. This study suggests that multivalent betulinic acid derivatives have possible use as a new class of influenza virus entry inhibitors.
. 2020 May 19.
doi: 10.1021/acs.molpharmaceut.0c00244. Online ahead of print.
Synthesis of a Hexavalent Betulinic Acid Derivative as a Hemagglutinin-Targeted Influenza Virus Entry Inhibitor
Yingying Chen, Xinchen Wang, Yinbiao Zhu, Longlong Si, Bo Zhang, Yongmin Zhang, Lihe Zhang, Demin Zhou, Sulong Xiao
- PMID: 32426985
- DOI: 10.1021/acs.molpharmaceut.0c00244
Abstract
Naturally occurring pentacyclic triterpenes, such as betulinic acid and its derivatives, exhibit various pharmaceutical activities and have been the subject of great interest, in particular for their antiviral properties. Here, we found a new anti-influenza virus conjugate, hexakis 6-deoxy-6-[4-N-(3β-hydroxy-lup-20(29)-en-28-oate)aminomethyl-1H-1,2,3-triazol-1-yl]-2,3-di-O-acetyl-α-cyclodextrin (CYY1-11, 1), in a minilibrary of pentacyclic triterpene-cyclodextrin conjugates by performing a cell-based screening assay and then exploring the underlying mechanisms. Our results showed that conjugate 1 possessed a high level activity against influenza virus A/WSN/33, with an IC50 value of 5.20 ?M (SI > 38.4). Study of the mechanism of action indicated that conjugate 1 inhibited viral replication by directly targeting the influenza hemagglutinin protein (KD = 1.50 ?M), thus efficiently preventing the attachment of the virion to its receptors on host cells and subsequent infection. This study suggests that multivalent betulinic acid derivatives have possible use as a new class of influenza virus entry inhibitors.