期刊
PHYTOCHEMISTRY
卷 203, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phytochem.2022.113392
关键词
Kopsia arborea Blume; Apocynaceae; Monoterpenoid indole alkaloids; Kopoffines A-C; Cyclin-dependent kinase 5; Tau phosphorylation
资金
- National Natural Science Foundation of China [81874295, 32170988, 31900737]
- Yunnan Revitalization Talents Support Plan-Young Talent Project
- DR PLANT, Basic Research Program of Yunnan Province [202201AW070010, 202001AT070107]
- Youth Innovation Promotion Association of CAS [2021000011]
- Original Innovation Project from 0 to 1 of the Basic Frontier Scientific Research Program, CAS [ZDBS-LY-SM031]
- CAS Light of West China Program [2020000023]
- Young scientific and technological talents promotion project of Yunnan Association for Science and Technology [2022000043]
Three novel monoterpenoid indole alkaloid dimers (kopoffines A-C) and nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Kopoffines A-C exhibited significant inhibition against cyclin-dependent kinase 5 and reduced the levels of phosphorylated Tau, which are involved in the formation of neurofibrillary tangles. These findings may have implications for the development of therapeutics for related diseases.
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.
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