Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity

A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (1–7) 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 an...

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Veröffentlicht in:Journal of natural products (Washington, D.C.) D.C.), 2024-05, Vol.87 (5), p.1376-1383
Hauptverfasser: Li, Zhengyuan, Chai, Ling, Tang, Zhenzhou, Zhu, Hongrui, Xue, Peiying, Sun, Fan, Lin, Houwen, Zhou, Yongjun, Lin, Xiao
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container_issue 5
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container_title Journal of natural products (Washington, D.C.)
container_volume 87
creator Li, Zhengyuan
Chai, Ling
Tang, Zhenzhou
Zhu, Hongrui
Xue, Peiying
Sun, Fan
Lin, Houwen
Zhou, Yongjun
Lin, Xiao
description A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (1–7) 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.
doi_str_mv 10.1021/acs.jnatprod.4c00013
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subjects Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
biosynthesis
colorectal neoplasms
cytotoxicity
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Mutation
Nuclear Magnetic Resonance, Biomolecular
Organic Chemicals
Streptomyces
Streptomyces - chemistry
Streptomyces - metabolism
title Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity
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