2,8-Dioxabicyclo[3.3.1]nonane 衍生物的合成及其神经保护活性

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI:10.1248/cpb.c23-00693

Hitoshi Kamauchi, Akifumi Takanashi, Mitsuaki Suzuki, Kouki Izumi, Koichi Takao, Yoshiaki Sugita

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引用次数: 0

摘要

研究人员合成了 20 种类似天然产物的 2,8-二氧双环[3.3.1]壬烷衍生物，并利用人体单胺氧化酶（MAO）A 和 B 以及乙酰胆碱酯酶（ChE）和丁酰胆碱酯酶（ChE）测试了它们的神经保护活性。化合物 1s 对 MAO-A、MAO-B 和乙酰胆碱酯酶（AChE）具有抑制活性（IC50 值分别为 34.0、2.3 和 11.0 µM）。研究了 (-)-1s 对 MAO-B 的抑制模式。(±)-1s的手性高效液相色谱分离了对映体，(-)-1s显示出对MAO-B的抑制活性。分子对接模拟揭示了(-)-1s与MAO-B的结合模式。

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Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Derivatives and Their Neuroprotective Activities

Twenty natural-product-like 2,8-dioxabicyclo[3.3.1]nonane derivatives were synthesized and their neuroprotective activities were tested using human monoamine oxidases (MAO) A and B and acetyl and butyryl cholinesterases (ChE). Compound 1s showed inhibitory activity for MAO-A, MAO-B and acetylcholinesterase (AChE) (IC₅₀ values 34.0, 2.3 and 11.0 µM, respectively). The inhibition mode of (−)-1s for MAO-B was investigated. Chiral HPLC of (±)-1s separated the enantiomers and (−)-1s showed MAO-B inhibitory activity. Molecular docking simulation of (−)-1s and MAO-B revealed the binding mode.

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来源期刊

Chemical & pharmaceutical bulletin 医学-化学综合

CiteScore

3.20

自引率

5.90%

发文量

132

审稿时长

1.7 months

期刊介绍： The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.