Monoterpenoid indole alkaloid dimers from Kopsia arborea inhibit cyclin-dependent kinase 5 and tau phosphorylation

被引：11

作者：

Chen, Chen ^{[1
]}

Liu, Jian-Wen ^{[1
]}

Guo, Ling-Li ^{[1
]}

Xiong, Feng ^{[1
]}

Ran, Xiao-Qian ^{[2
,3
,5
]}

Guo, Ya-Rong ^{[2
,3
,6
]}

Yao, Yong-Gang ^{[2
,3
,5
]}

Hao, Xiao-Jiang ^{[1
,4
]}

Luo, Rong-Can ^{[2
,3
,5
]}

Zhang, Yu ^{[1
]}

机构：

[1] Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Chi, Kunming 650201, Yunnan, Peoples R China

[2] Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming 650204, Yunnan, Peoples R China

[3] Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common D, Kunming 650204, Yunnan, Peoples R China

[4] Chinese Acad Med Sci, Res Unit Chem Biol Nat Antivirus Prod, Beijing 100730, Peoples R China

[5] Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650201, Yunnan, Peoples R China

[6] Univ Sci & Technol China, Sch Life Sci, Div Life Sci & Med, Hefei 230026, Anhui, Peoples R China

来源：

PHYTOCHEMISTRY | 2022年 / 203卷

基金：

中国国家自然科学基金;

关键词：

Kopsia arborea Blume; Apocynaceae; Monoterpenoid indole alkaloids; Kopoffines A-C; Cyclin-dependent kinase 5; Tau phosphorylation; ALZHEIMERS-DISEASE; BISINDOLE ALKALOIDS; A-I; CDK5; NEURODEGENERATION; RHAZINILAM; NEURONS;

D O I：

10.1016/j.phytochem.2022.113392

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Three undescribed monoterpenoid indole alkaloid dimers (kopoffines A-C, which are connected via a methylene unit) and with nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Their structures, including their absolute configurations, were established by HRESIMS, NMR, single-crystal X-ray diffraction, and ECD analyses. Kopoffines A-C showed significant inhibition against cyclin-dependent kinase 5 (IC50: 0.34-2.18 mu M). Western blotting analyses showed that kopoffines A-C significantly decreased the protein levels of CDK5 and phospho-CDK5 (Tyr15) (pCDK5) at concentrations of 2.5 and 10 mu M. The levels of phospho-Tau (Thr217) (pTau217, a new biomarker of AD), and phospho-Tau (Ser396) (pTau396), which play major roles in the formation of neurofibrillary tangles , were decreased by the kopoffines A-C treatment. Molecular docking studies indicated that kopoffines A-C could form stable interactions with CDK5.

引用

页数：11

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