Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity

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
Format: Artikel
Sprache:eng
Schlagworte:
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
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Zusammenfassung: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.
ISSN:0163-3864
1520-6025
1520-6025
DOI:10.1021/acs.jnatprod.4c00013