Structure-activity relationships of 3-O-β-chacotriosyl ursolic acid derivatives as novel H5N1 entry inhibitors.
A series of methyl ursolate 3-O-β-chacotrioside analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 3 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 3 indicated that both the type of pentacyclic triterpene and the subtle modification of ursolic acid as an aglycon had key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of ursolic acid or alteration of the C-3 configuration of ursolic acid from 3β-to 3α-forms was helpful to significantly improve the selective index while keeping their antiviral activities.
College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China. Electronic address: vinsin1021@126.com.
Gaopeng
G
Song
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Xintian
X
Shen
Department of Human Anatomy, School of Medicine, Jinan University, Guangzhou, 510632, China.
Sumei
S
Li
College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.
Yibin
Y
Li
Center for Diagnostics and Therapeutics, Department of Chemistry, Georgia State University, Atlanta, GA, 30303, United States.
Yunpeng
Y
Liu
College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.
Yushan
Y
Zheng
College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.
Ruheng
R
Lin
College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.
Jihong
J
Fan
College of Resources and Environment, South China Agricultural University, Guangzhou, 510642, China.
Hanming
H
Ye
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. Electronic address: liusw@smu.edu.cn.
Shuwen
S
Liu
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D014326:Tropanes / Q000737:chemistry*; D053586:Virus Internalization / Q000187:drug effects*; D000097245:Ursolic Acid
D000998:Antiviral Agents; D014315:Triterpenes; D014326:Tropanes; D000097245:Ursolic Acid; C433845:chacotriose
3-O-β-chacotriosyl saponins; H5N1 entry inhibitors; Structure–activity relationships