KIB OpenIR
Synthesis of nigranoic acid and manwuweizic acid derivatives as HDAC inhibitors and anti-inflammatory agents
Ni,Dong-Xuan; Wang,Qi; Li,Yi-Ming; Cui,Yi-Man; Shen,Tian-Ze; Li,Xiao-Li; Sun,Han-Dong; Zhang,Xing-Jie; Zhang,Ruihan; Xiao,Wei-Lie
2021
发表期刊BIOORGANIC CHEMISTRY
ISSN0045-2068
卷号109页码:104728
摘要As a successful anti-tumor drug target, the family of histone deacetylases (HDACs) is also a critical player in immune response, making the research of anti-inflammatory HDAC inhibitors an attractive new focus. In this report, triterpenoids nigranoic acid (NA) and manwuweizic acid (MA) were identified as HDAC inhibitors through docking-based virtual screening and enzymatic activity assay. A series of derivatives of NA and MA were synthesized and assessed for their biological effects. As a result, hydroxamic acid derivatives of NA and MA showed moderately increased activity for HDAC1/2/4/6 inhibition (the lowest IC50 against HDAC1 is 1.14 ?M), with no activity against HDAC8. In J774A.1 macrophage, compound 1?3, 13 and 17?19 demonstrated inhibitory activity against lactate dehydrogenase (LDH) and IL-113 production, without affecting cell viability. Compound 19 increased the histone acetylation level in J774A.1 cells, as well as inhibited IL-113 maturation and caspase-1 cleavage. These results indicated that compound 19 blocks the activation of NLRP3 inflammasome, probably related to HDAC inhibition. This work provided a natural scaffold for developing low-cytotoxic and antiinflammatory HDAC inhibitors, as well as a class of tool molecules for studying the relationship between HDACs and NLRP3 activation.
关键词Natural products modification HDAC inhibition Inflammasome Triterpenoid SCHISANDRA-PROPINQUA TRITERPENOIDS MECHANISM INJURY
DOI10.1016/j.bioorg.2021.104728
WOS记录号WOS:000639153600008
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/73498
专题中国科学院昆明植物研究所
作者单位1.[Ni, Dong-Xuan
2.Wang, Qi
3.Li, Yi-Ming
4.Cui, Yi-Man
5.Shen, Tian-Ze
6.Li, Xiao-Li
7.Zhang, Xing-Jie
8.Zhang, Ruihan
9.Yunnan Univ, Yunnan Res & Dev Ctr Nat Prod, Sch Chem Sci & Technol, Key Lab Med Chem Nat Resource,Minist Educ, Kunming 650091, Yunnan, Peoples R China
10.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
推荐引用方式
GB/T 7714
Ni,Dong-Xuan,Wang,Qi,Li,Yi-Ming,et al. Synthesis of nigranoic acid and manwuweizic acid derivatives as HDAC inhibitors and anti-inflammatory agents[J]. BIOORGANIC CHEMISTRY,2021,109:104728.
APA Ni,Dong-Xuan.,Wang,Qi.,Li,Yi-Ming.,Cui,Yi-Man.,Shen,Tian-Ze.,...&Xiao,Wei-Lie.(2021).Synthesis of nigranoic acid and manwuweizic acid derivatives as HDAC inhibitors and anti-inflammatory agents.BIOORGANIC CHEMISTRY,109,104728.
MLA Ni,Dong-Xuan,et al."Synthesis of nigranoic acid and manwuweizic acid derivatives as HDAC inhibitors and anti-inflammatory agents".BIOORGANIC CHEMISTRY 109(2021):104728.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Ni,Dong-Xuan]的文章
[Wang,Qi]的文章
[Li,Yi-Ming]的文章
百度学术
百度学术中相似的文章
[Ni,Dong-Xuan]的文章
[Wang,Qi]的文章
[Li,Yi-Ming]的文章
必应学术
必应学术中相似的文章
[Ni,Dong-Xuan]的文章
[Wang,Qi]的文章
[Li,Yi-Ming]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。