Synthesis of nature product kinsenoside analogues with anti-inflammatory activity

Wei Song; Yong Sun; Lintao Xu; Yajing Sun; Tianlu Li; Peng Peng; Hongxiang Lou

doi:10.1016/j.bmc.2020.115854

Synthesis of nature product kinsenoside analogues with anti-inflammatory activity

Bioorg Med Chem. 2021 Jan 1:29:115854. doi: 10.1016/j.bmc.2020.115854. Epub 2020 Nov 13.

Authors

Wei Song¹, Yong Sun¹, Lintao Xu¹, Yajing Sun², Tianlu Li³, Peng Peng⁴, Hongxiang Lou⁵

Affiliations

¹ Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
² National Glycoengineering Research Center, Shandong University, Jinan 250012, PR China.
³ Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China; National Glycoengineering Research Center, Shandong University, Jinan 250012, PR China.
⁴ National Glycoengineering Research Center, Shandong University, Jinan 250012, PR China. Electronic address: pengpeng@sdu.edu.cn.
⁵ Key Laboratory of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China. Electronic address: louhongxiang@sdu.edu.cn.

PMID: 33223464
DOI: 10.1016/j.bmc.2020.115854

Abstract

Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.

Keywords: Anti-inflammatory; Goodyeroside A; Kinsenoside; Nitric Oxide Release; Structure-activity Relationship.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Butyrolactone / analogs & derivatives*
4-Butyrolactone / chemical synthesis
4-Butyrolactone / chemistry
4-Butyrolactone / pharmacology
Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Biological Products / chemical synthesis
Biological Products / chemistry
Biological Products / pharmacology*
Cell Survival / drug effects
Dose-Response Relationship, Drug
Inflammation / drug therapy*
Inflammation / metabolism
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Molecular Structure
Monosaccharides / chemical synthesis
Monosaccharides / chemistry
Monosaccharides / pharmacology*
NF-kappa B / antagonists & inhibitors*
NF-kappa B / metabolism
Nitric Oxide / antagonists & inhibitors
Nitric Oxide / biosynthesis
RAW 264.7 Cells
Signal Transduction / drug effects
Structure-Activity Relationship

Substances

3-glucopyranosyloxybutanolide
Anti-Inflammatory Agents, Non-Steroidal
Biological Products
Lipopolysaccharides
Monosaccharides
NF-kappa B
Nitric Oxide
4-Butyrolactone