Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity

IF 3.3 2区 生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2024-04-25 DOI:10.1021/acs.jnatprod.4c00013
Zhengyuan Li, Ling Chai, Zhenzhou Tang, Hongrui Zhu, Peiying Xue, Fan Sun, Houwen Lin, Yongjun Zhou* and Xiao Lin*, 
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Abstract

A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (17) from Streptomyces conglobatus RJ2. Structure elucidation was conducted using NMR and HRESIMS analysis, and the absolute configuration was determined by advanced Marfey’s method, Mosher’s analysis, and ECD analysis. The obtained compounds revealed selective and significant cytotoxicity, specifically against colorectal cancer cells bearing the K-ras mutation, with IC50 values ranging from 40 nM to 3.5 μM.

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具有选择性细胞毒性的新安霉素衍生物的前体定向生物合成。
通过前体引导的生物合成方法,从链霉菌 RJ2 中积累了七种新安替比林衍生物(1-7)。利用核磁共振和 HRESIMS 分析进行了结构阐释,并通过先进的 Marfey 方法、Mosher 分析和 ECD 分析确定了绝对构型。所获得的化合物具有选择性和显著的细胞毒性,特别是对带有 K-ras 突变的结直肠癌细胞,其 IC50 值从 40 nM 到 3.5 μM 不等。
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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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