Synthesis and anti-inflammatory activity of mogrol derivatives modified at C 24 sitee

被引：0

作者：

Song, Jing-Ru ^{[1
]}

Wei, Yu-Lu ^{[1
]}

Jiang, Xiao-Hua ^{[1
]}

Fang, Xiu-Yun ^{[1
]}

Yang, Xue-Rong ^{[1
]}

Li, Dian-Peng ^{[2
]}

机构：

[1] Guangxi Zhuang Autonomous Reg & Chinese Acad Sci, Guangxi Inst Bot, Guangxi Key Lab Plant Funct Phytochem & Sustainabl, Guilin, Peoples R China

[2] Guangxi Univ Chinese Med, Engn Res Ctr Innovat Tradit Chinese, Zhuang & Yao Mat Med, Minist Educ, Nanning, Peoples R China

来源：

FITOTERAPIA | 2024年 / 176卷

关键词：

Siraitia grosvenorii; Mogrol; Derivatives; Anti-inflammatory; TLR4/NF-kappa B/iNOS; NITRIC-OXIDE;

D O I：

10.1016/j.fitote.2024.106005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Mogrol, the aglycone of well-known sweeter mogrosides, shows potent anti-inflammatory activity. In this study, forty-two mogrol derivatives bearing various pharmacophores with oxygen or nitrogen atoms were designed and synthesized via structural modification at C 24 site, and their anti-inflammatory activity were screened against lipopolysaccharide (LPS)-induced RAW264.7 cells. Compared with mogrol, most of derivatives exhibited stronger inhibition of NO production without cytotoxicity. In particular, compound B5 that contained an indole motif effectively suppressed the secretion of inflammatory mediators including TNF-alpha and IL -6, and inhibited the expression levels of TLR4, p -p65 and iNOS proteins. Molecular docking showed that the active B5 interacted with amino acid residues of iNOS protein through n -n stacking and hydrophobic interactions with binding affinity value of -12.1 kcal/mol, which was much stronger than mogrol (-8.9 kcal/mol). These results suggest that derivative B5 is a promising anti-inflammatory molecule and the strategy of hybridizing indole skeleton on mogrol is worthy for further attention.

引用

页数：12

共 27 条

[1] Anti-inflammatory efficacy and relevant SAR investigations of novel chiral pyrazolo isoquinoline derivatives: Design, synthesis, in-vitro, in-vivo, and computational studies targeting iNOS [J].