| Title | Synthesis of a Hexavalent Betulinic Acid Derivative as a Hemagglutinin-Targeted Influenza Virus Entry Inhibitor |
| Authors | Chen, Yingying Wang, Xinchen Zhu, Yinbiao Si, Longlong Zhang, Bo Zhang, Yongmin Zhang, Lihe Zhou, Demin Xiao, Sulong |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA Chinese Acad Med Sci & Peking Union Med Coll, Med Res Ctr, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China Sorbonne Univ, Inst Parisien Chim Mol, CNRS, UMR 8232, F-75005 Paris, France |
| Keywords | ANTI-AIDS AGENTS HIV-1 MATURATION INHIBITOR PENTACYCLIC TRITERPENOIDS BEVIRIMAT AGGLUTINATION ERYTHROCYTES BMS-955176 DISCOVERY SPECTRUM ANALOGS |
| Issue Date | 6-Jul-2020 |
| Publisher | MOLECULAR PHARMACEUTICS |
| Abstract | Naturally occurring pentacyclic triterpenes, such as betulinic acid (BA) 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-(3 beta-hydroxy-lup-20 (29) -en -28-oate) aminomethyl- 1H-1, 2,3-triazol-1-yl] -2,3-di-O-acetyl-alpha-cyclodextrin (CYY1-11, 1), in a mini library 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 the influenza virus A/WSN/33 with an IC(50 )value of 5.20 mu M (SI > 38.4). The study of the mechanism of action indicated that conjugate 1 inhibited viral replication by directly targeting the influenza hemagglutinin protein (K-D = 1.50 mu M), thus efficiently preventing the attachment of the virion to its receptors on host cells and subsequent infection. This study suggests that multivalent BA derivatives have possible use as a new class of influenza virus entry inhibitors. |
| URI | http://hdl.handle.net/20.500.11897/617325 |
| ISSN | 1543-8384 |
| DOI | 10.1021/acs.molpharmaceut.0c00244 |
| Indexed | SCI(E) |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
