Structure-Aided Optimization Of 3-O-Beta-Chacotriosyl Epiursolic Acid Derivatives As Novel H5n1 Virus Entry Inhibitors
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS(2020)
摘要
It is urgent to develop new antiviral agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene saponins with 3-O-beta-chacotriosyl residue are novel H5N1 virus entry inhibitors. In the present study, a series of C-28 modified 3-O-beta-chacotriosyl epiursolic acid derivatives via conjugation with different kinds of sides were synthesized, of which anti-H5N1 activities in A549 cells were evaluated in vitro. Among them, 10 exhibited strongest anti-H5N1 potency at the low-micromole level without cytotoxicity, surpassing the potency of ribavirin. Further mechanism studies of the lead compound 10 based on HI, SPR and molecular modeling revealed that these new 3-epiursolic acid saponins could bind tightly to the viral envelope HA protein, thus blocking the invasion of H5N1 viruses into host cells.
更多查看译文
关键词
3-Epiursolic acid saponins, Semi-synthesis, H5N1 entry inhibitors, Structure-activity relationships
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络