沉默互变异构从小绒泡菌中分离不稳定的绒泡蛋白

IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2022-05-24 DOI:10.1021/acs.jnatprod.2c00101
Jiang-Ping Wu, Ling-Yu Li, Jing-Rong Li, Meng Yu, Jianping Zhao, Qiong-Ming Xu, Yu-Cheng Gu, Tao Zhang* and Zhong-Mei Zou*, 
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引用次数: 4

摘要

一些物理磷脂固有的结构不稳定性阻碍了这些化合物的分离和鉴定,大约50年来,仍然没有一种有效的方法来克服这些挑战。在本研究中,通过同位素标记实验和DFT计算,阐明了不稳定physalins前所未有的互变异构机制,从而首次成功分离了互变异构体并分离出高纯度的产物。结果表明,从Physalis minima L.植物中分离到了15个新的physalins,即physaminins a - o(1-15)和17个已知的类似物(16-32)。通过对光谱数据的综合分析,确定了新化合物的化学结构,并通过计算ECD计算和/或单晶x射线衍射分析确定了它们的绝对构型。所有获得的分离物对四种人类癌细胞系(A549、HepG2、MCF-7和SCG-7901)和两种非癌细胞系(RAW 264.7和人正常肝细胞L02)的抗增殖作用进行了评估,并通过测量其体外抑制lps刺激小鼠RAW 264.7细胞NO生成的能力来评估其抗炎活性。化合物1 ~ 5、13、16、18、19、23和30对4种人类癌细胞均有显著的抑制增殖作用,IC50值在0.2(0)~ 24.7(2)μM之间,且在10 μM浓度下对2种非癌细胞无毒性。化合物7、10、11、12、14、17、22和27显著抑制NO生成,IC50值在2.9(1)~ 9.5(2)μM之间。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Silencing Tautomerization to Isolate Unstable Physalins from Physalis minima

The inherent structural instability of some physalins has hampered the isolation and identification of these compounds for approximately 50 years, and an effective method to overcome these challenges remains unavailable. In the present study, the unprecedented tautomerization mechanism of unstable physalins was elucidated by performing isotopic labeling experiments and DFT calculations, which led to the successful separation of tautomers and isolation of highly pure products for the first time. As a result, 15 new physalins, physaminins A–O (115), as well as 17 known analogues (1632), were isolated from the whole plants of Physalis minima L. The chemical structures of the new compounds were established by performing a comprehensive analysis of spectroscopic data, and their absolute configurations were confirmed by using computational ECD calculations and/or single-crystal X-ray diffraction analyses. All obtained isolates were evaluated for their antiproliferative effects against four human cancer cell lines (A549, HepG2, MCF-7, and SCG-7901) and two noncancerous cell lines (RAW 264.7 and human normal hepatocytes L02), as well as their anti-inflammatory activities by measuring their abilities to inhibit NO production in LPS-stimulated murine RAW 264.7 cells in vitro. Compounds 15, 13, 16, 18, 19, 23, and 30 exerted significant antiproliferative effects on the four human cancer lines, with IC50 values ranging from 0.2(0) to 24.7(2) μM, and these compounds were not toxic to the two noncancerous cell lines at a concentration of 10 μM. Moreover, compounds 7, 10, 11, 12, 14, 17, 22, and 27 significantly inhibited NO production, with IC50 values ranging from 2.9(1) to 9.5(2) μM.

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来源期刊
CiteScore
9.10
自引率
5.90%
发文量
294
审稿时长
2.3 months
期刊介绍: The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
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