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A Grand Challenge. 3. Unbiased Phenotypic Function of Metabolites from Australia Plants Gloriosa superba and Alangium villosum against Parkinson's Disease.
Journal of Natural Products ( IF 5.1 ) Pub Date : 2020-05-06 , DOI: 10.1021/acs.jnatprod.9b00880
Dongdong Wang 1 , Mariyam Murtaza 1 , Stephen A Wood 1 , George D Mellick 1 , William Gang Miao 1 , Gordon P Guymer 2 , Paul I Forster 2 , Yunjiang Feng 1 , Ronald J Quinn 1
Affiliation  

As part of a continuing research program aiming to identify chemical probes to interrogate Parkinson's disease (PD), we have investigated the Australian plants Gloriosa superba and Alangium villosum. The chemical investigations of G. superba resulted in the isolation of four new alkaloids, β-lumicolchicosides A-C (1-3) and γ-lumicolchicoside A (4), together with four lumicolchicine derivatives (5-8) and six colchicine analogues (9-14) as known structures. The chemical investigations of A. villosum resulted in the isolation of four new benzoquinolizidine N-oxides, tubulosine Nβ5-oxide (15), isotubulosine Nα5-oxide (16), 9-demethyltubulosine Nβ5-oxide (17), and 9-demethylisotubulosine Nα5-oxide (18), together with five known benzoquinolizidine alkaloids (19-23). The chemical structures of the new compounds (1-4 and 15-18) were characterized unambiguously by extensive analysis of their NMR and MS data. Unbiased multidimensional profiling was used to investigate the phenotypic profiles of all of the metabolites. The results show that the lead probes have different effects on cellular organelles that are implicated in PD in patient-derived cells.

中文翻译:

大挑战。3.来自澳大利亚的植物格劳萨(Gloriosa superba)和绒毛芋(Alangium v​​illosum)的代谢物对帕金森氏病的无偏见表型功能。

作为旨在识别可探究帕金森氏病(PD)的化学探针的一项持续研究计划的一部分,我们对澳大利亚植物Gloriosa superba和Alangium v​​illosum进行了调查。对G. superba进行化学研究后,分离出了四种新生物碱,β-lumicolchicosidesAC(1-3)和γ-lumicolchicosideA(4),以及四种lumicolchicine衍生物(5-8)和六个秋水仙碱类似物(9)。 -14)作为已知结构。绒毛青霉的化学研究导致分离出四种新的苯并喹啉氮氧化物,微管素Nβ5-氧化物(15),异微管素Nα5-氧化物(16),9-去甲基微管素Nβ5-氧化物(17)和9-去甲基异微管素Nα5 -氧化物(18),以及五种已知的苯并喹喔啉生物碱(19-23)。通过广泛分析其NMR和MS数据,明确表征了新化合物(1-4和15-18)的化学结构。无偏多维分析用于研究所有代谢物的表型特征。结果表明,铅探针对涉及患者来源细胞中PD的细胞器有不同的作用。
更新日期:2020-05-06
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