Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol derivatives as alpha-glucosidase and PTP1B inhibitors

doi:10.1007/s00044-021-02836-0

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	Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol derivatives as alpha-glucosidase and PTP1B inhibitors
	Yang, Xiao-Tong; Li, Tian-Ze; Geng, Chang-An; Liu, Pei; Chen, Ji-Jun
	2022
发表期刊	MEDICINAL CHEMISTRY RESEARCH
卷号	31 期号:2 页码:350-367
摘要	The dammarane triterpenoid (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol obtained from Cyclocarya paliurus in our previous study showed inhibitory activity on alpha-glucosidase in vitro with an inhibitory ratio of 32.2% at the concentration of 200 mu M. In order to reveal the structure-activity relationships (SARs) and get more active compounds, 42 derivatives of (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol were synthesized by chemical modification on the hydroxyls (C-3 and C-12), rings A and E, and assayed for their alpha-glucosidase and PTP1B inhibitory activities. Two compounds (8, 26) increased activity against alpha-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both alpha-glucosidase and PTP1B as dual-target inhibitors with IC50 values of 489.8, 467.7 mu M (alpha-glucosidase) and 319.7, 269.1 mu M (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on alpha-glucosidase and a noncompetitive-type inhibitor on PTP1B based on enzyme kinetic study. Furthermore, compound 42 could selectively inhibited PTP1B as a mix-type inhibitor with IC50 value of 134.9 mu M, which was 2.5-fold higher than the positive control, suramin sodium (IC50 339.0 mu M), but not inhibit alpha-glucosidase. [GRAPHICS] .
关键词	(20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol alpha-glucosidase inhibitors PTP1B inhibitors Enzyme kinetics TYROSINE-PHOSPHATASE 1B DIABETES-MELLITUS EPIDEMIOLOGY
DOI	10.1007/s00044-021-02836-0
收录类别	SCI
WOS记录号	WOS:000741244600001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74645
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Yang, Xiao-Tong,Li, Tian-Ze,Geng, Chang-An,et al. Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol derivatives as alpha-glucosidase and PTP1B inhibitors[J]. MEDICINAL CHEMISTRY RESEARCH,2022,31(2):350-367.
APA	Yang, Xiao-Tong,Li, Tian-Ze,Geng, Chang-An,Liu, Pei,&Chen, Ji-Jun.(2022).Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol derivatives as alpha-glucosidase and PTP1B inhibitors.MEDICINAL CHEMISTRY RESEARCH,31(2),350-367.
MLA	Yang, Xiao-Tong,et al."Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3 beta,12 beta,25-triol derivatives as alpha-glucosidase and PTP1B inhibitors".MEDICINAL CHEMISTRY RESEARCH 31.2(2022):350-367.

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