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 |
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container_title | Journal of natural products (Washington, D.C.) |
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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 |
format | Article |
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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.</description><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>biosynthesis</subject><subject>colorectal neoplasms</subject><subject>cytotoxicity</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Humans</subject><subject>Molecular Structure</subject><subject>Mutation</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Organic Chemicals</subject><subject>Streptomyces</subject><subject>Streptomyces - chemistry</subject><subject>Streptomyces - metabolism</subject><issn>0163-3864</issn><issn>1520-6025</issn><issn>1520-6025</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAQRS0EgvL4A4SyZJMyzsRusoSWl4QACRDLyHEmwqiNwXaA_D2GFpawmofOnZEOY_scxhwyfqS0Hz93Krw424xzDQAc19iIiwxSCZlYZyPgElMsZL7Ftr1_jghCKTbZVtzJDMtixB5vHeneeevSmYltoCY5MdYPXXgib3xi2-SarOqCWQzadMmMnHlTwbyRT95NeEruaB5jcU6mQ7DBfhhtwrDLNlo197S3qjvs4ez0fnqRXt2cX06Pr1KFCCFtBRZN2-TNpBAKqclEjaVWtSrVJCtI61bKHHieT9q6QaEROGlBUNaAss5a3GGHy7tRw2tPPlQL4zXN56oj2_sKuUAJHJD_j0IuBZ9EQxHNl6h21ntHbfXizEK5oeJQfdmvov3qx361sh9jB6sPfb2g5jf0ozsCsAS-47Z3XXTz981PXYCWLA</recordid><startdate>20240524</startdate><enddate>20240524</enddate><creator>Li, Zhengyuan</creator><creator>Chai, Ling</creator><creator>Tang, Zhenzhou</creator><creator>Zhu, Hongrui</creator><creator>Xue, Peiying</creator><creator>Sun, Fan</creator><creator>Lin, Houwen</creator><creator>Zhou, Yongjun</creator><creator>Lin, Xiao</creator><general>American Chemical Society and American Society of Pharmacognosy</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-7097-0876</orcidid><orcidid>https://orcid.org/0000-0002-3005-2843</orcidid><orcidid>https://orcid.org/0000-0001-7278-2062</orcidid></search><sort><creationdate>20240524</creationdate><title>Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity</title><author>Li, Zhengyuan ; Chai, Ling ; Tang, Zhenzhou ; Zhu, Hongrui ; Xue, Peiying ; Sun, Fan ; Lin, Houwen ; Zhou, Yongjun ; Lin, Xiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a330t-f538dfd4d785a3ed25b39caba9a728eccf66401447fbd35c301ec5e09b036b2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>biosynthesis</topic><topic>colorectal neoplasms</topic><topic>cytotoxicity</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Humans</topic><topic>Molecular Structure</topic><topic>Mutation</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Organic Chemicals</topic><topic>Streptomyces</topic><topic>Streptomyces - chemistry</topic><topic>Streptomyces - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Zhengyuan</creatorcontrib><creatorcontrib>Chai, Ling</creatorcontrib><creatorcontrib>Tang, Zhenzhou</creatorcontrib><creatorcontrib>Zhu, Hongrui</creatorcontrib><creatorcontrib>Xue, Peiying</creatorcontrib><creatorcontrib>Sun, Fan</creatorcontrib><creatorcontrib>Lin, Houwen</creatorcontrib><creatorcontrib>Zhou, Yongjun</creatorcontrib><creatorcontrib>Lin, Xiao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Journal of natural products (Washington, D.C.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zhengyuan</au><au>Chai, Ling</au><au>Tang, Zhenzhou</au><au>Zhu, Hongrui</au><au>Xue, Peiying</au><au>Sun, Fan</au><au>Lin, Houwen</au><au>Zhou, Yongjun</au><au>Lin, Xiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity</atitle><jtitle>Journal of natural products (Washington, D.C.)</jtitle><addtitle>J. Nat. Prod</addtitle><date>2024-05-24</date><risdate>2024</risdate><volume>87</volume><issue>5</issue><spage>1376</spage><epage>1383</epage><pages>1376-1383</pages><issn>0163-3864</issn><issn>1520-6025</issn><eissn>1520-6025</eissn><abstract>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. 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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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