Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007
Metarhizin C, a stereoisomer of BR-050 was isolated from a fungus Tolypocladium album RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry...
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| Veröffentlicht in: | Journal of antibiotics 2019-12, Vol.72 (12), p.996-1000 |
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| container_title | Journal of antibiotics |
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| creator | Nogawa, Toshihiko Kawatani, Makoto Okano, Akiko Futamura, Yushi Aono, Harumi Shimizu, Takeshi Kato, Naoki Kikuchi, Haruhisa Osada, Hiroyuki |
| description | Metarhizin C, a stereoisomer of BR-050 was isolated from a fungus
Tolypocladium album
RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry, and found to be identical to that of 3-desacylmetarhizin A with the absolute structure. Previously, it had been isolated by Kikuchi et al and proposed as BR-050 including the stereo-structure. However, detailed analysis for the newly isolated isomer confirmed that 3-desacylmetarhizin A was not identical to BR-050. Therefore, we assigned it metarhizin C as a new BR-050 isomer. Metarhizin C showed selective cytotoxicity against osteosarcoma MG-63 cells in a glucose independent condition with IC
50
value of 0.79 µg/ml, while > 30 µg/ml of IC
50
value in a normal condition, and inhibited a mitochondrial respiration. |
| doi_str_mv | 10.1038/s41429-019-0229-1 |
| format | Article |
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Tolypocladium album
RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry, and found to be identical to that of 3-desacylmetarhizin A with the absolute structure. Previously, it had been isolated by Kikuchi et al and proposed as BR-050 including the stereo-structure. However, detailed analysis for the newly isolated isomer confirmed that 3-desacylmetarhizin A was not identical to BR-050. Therefore, we assigned it metarhizin C as a new BR-050 isomer. Metarhizin C showed selective cytotoxicity against osteosarcoma MG-63 cells in a glucose independent condition with IC
50
value of 0.79 µg/ml, while > 30 µg/ml of IC
50
value in a normal condition, and inhibited a mitochondrial respiration.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/s41429-019-0229-1</identifier><identifier>PMID: 31481762</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/47 ; 101/58 ; 101/6 ; 631/92/349 ; 631/92/613 ; 82/16 ; Animals ; Antimalarials - chemistry ; Antimalarials - pharmacology ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Bacteriology ; Biomedical and Life Sciences ; Bioorganic Chemistry ; Bone cancer ; Bone Neoplasms - drug therapy ; Bone Neoplasms - pathology ; Cytotoxicity ; Diterpenes - chemistry ; Drug Screening Assays, Antitumor ; Humans ; Hypocreales - chemistry ; Hypocreales - isolation & purification ; Hypocreales - metabolism ; Life Sciences ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Medicinal Chemistry ; Microbial Sensitivity Tests ; Microbiology ; Molecular Structure ; Organic Chemistry ; Osteosarcoma - drug therapy ; Osteosarcoma - pathology ; Rats ; Sarcoma ; Soil Microbiology ; Special Feature: Brief Communication ; Stereoisomerism</subject><ispartof>Journal of antibiotics, 2019-12, Vol.72 (12), p.996-1000</ispartof><rights>The Author(s), under exclusive licence to the Japan Antibiotics Research Association 2019</rights><rights>Copyright Nature Publishing Group Dec 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-5f9d19e4af4ac8a54d745d3e1712e3b79212d7efbb954a7a2c1dd8d29b42dee33</citedby><cites>FETCH-LOGICAL-c462t-5f9d19e4af4ac8a54d745d3e1712e3b79212d7efbb954a7a2c1dd8d29b42dee33</cites><orcidid>0000-0003-4410-4090 ; 0000-0001-6938-0185 ; 0000-0003-1270-5270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31481762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nogawa, Toshihiko</creatorcontrib><creatorcontrib>Kawatani, Makoto</creatorcontrib><creatorcontrib>Okano, Akiko</creatorcontrib><creatorcontrib>Futamura, Yushi</creatorcontrib><creatorcontrib>Aono, Harumi</creatorcontrib><creatorcontrib>Shimizu, Takeshi</creatorcontrib><creatorcontrib>Kato, Naoki</creatorcontrib><creatorcontrib>Kikuchi, Haruhisa</creatorcontrib><creatorcontrib>Osada, Hiroyuki</creatorcontrib><title>Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>Metarhizin C, a stereoisomer of BR-050 was isolated from a fungus
Tolypocladium album
RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry, and found to be identical to that of 3-desacylmetarhizin A with the absolute structure. Previously, it had been isolated by Kikuchi et al and proposed as BR-050 including the stereo-structure. However, detailed analysis for the newly isolated isomer confirmed that 3-desacylmetarhizin A was not identical to BR-050. Therefore, we assigned it metarhizin C as a new BR-050 isomer. Metarhizin C showed selective cytotoxicity against osteosarcoma MG-63 cells in a glucose independent condition with IC
50
value of 0.79 µg/ml, while > 30 µg/ml of IC
50
value in a normal condition, and inhibited a mitochondrial respiration.</description><subject>101/47</subject><subject>101/58</subject><subject>101/6</subject><subject>631/92/349</subject><subject>631/92/613</subject><subject>82/16</subject><subject>Animals</subject><subject>Antimalarials - chemistry</subject><subject>Antimalarials - pharmacology</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Bacteriology</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Bone Neoplasms - pathology</subject><subject>Cytotoxicity</subject><subject>Diterpenes - chemistry</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Humans</subject><subject>Hypocreales - chemistry</subject><subject>Hypocreales - isolation & purification</subject><subject>Hypocreales - metabolism</subject><subject>Life Sciences</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Mass Spectrometry</subject><subject>Medicinal Chemistry</subject><subject>Microbial Sensitivity Tests</subject><subject>Microbiology</subject><subject>Molecular Structure</subject><subject>Organic Chemistry</subject><subject>Osteosarcoma - 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Academic</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nogawa, Toshihiko</au><au>Kawatani, Makoto</au><au>Okano, Akiko</au><au>Futamura, Yushi</au><au>Aono, Harumi</au><au>Shimizu, Takeshi</au><au>Kato, Naoki</au><au>Kikuchi, Haruhisa</au><au>Osada, Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007</atitle><jtitle>Journal of antibiotics</jtitle><stitle>J Antibiot</stitle><addtitle>J Antibiot (Tokyo)</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>72</volume><issue>12</issue><spage>996</spage><epage>1000</epage><pages>996-1000</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><abstract>Metarhizin C, a stereoisomer of BR-050 was isolated from a fungus
Tolypocladium album
RK17-F0007 through a screening program to search for new antitumor compounds. A structure of the isomer was determined by spectroscopic methods including detailed analysis of NOESY correlation and mass spectrometry, and found to be identical to that of 3-desacylmetarhizin A with the absolute structure. Previously, it had been isolated by Kikuchi et al and proposed as BR-050 including the stereo-structure. However, detailed analysis for the newly isolated isomer confirmed that 3-desacylmetarhizin A was not identical to BR-050. Therefore, we assigned it metarhizin C as a new BR-050 isomer. Metarhizin C showed selective cytotoxicity against osteosarcoma MG-63 cells in a glucose independent condition with IC
50
value of 0.79 µg/ml, while > 30 µg/ml of IC
50
value in a normal condition, and inhibited a mitochondrial respiration.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31481762</pmid><doi>10.1038/s41429-019-0229-1</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0003-4410-4090</orcidid><orcidid>https://orcid.org/0000-0001-6938-0185</orcidid><orcidid>https://orcid.org/0000-0003-1270-5270</orcidid></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of antibiotics, 2019-12, Vol.72 (12), p.996-1000 |
| issn | 0021-8820 1881-1469 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 101/47 101/58 101/6 631/92/349 631/92/613 82/16 Animals Antimalarials - chemistry Antimalarials - pharmacology Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Bacteriology Biomedical and Life Sciences Bioorganic Chemistry Bone cancer Bone Neoplasms - drug therapy Bone Neoplasms - pathology Cytotoxicity Diterpenes - chemistry Drug Screening Assays, Antitumor Humans Hypocreales - chemistry Hypocreales - isolation & purification Hypocreales - metabolism Life Sciences Magnetic Resonance Spectroscopy Mass Spectrometry Medicinal Chemistry Microbial Sensitivity Tests Microbiology Molecular Structure Organic Chemistry Osteosarcoma - drug therapy Osteosarcoma - pathology Rats Sarcoma Soil Microbiology Special Feature: Brief Communication Stereoisomerism |
| title | Structure and biological activity of Metarhizin C, a stereoisomer of BR-050 from Tolypocladium album RK17-F0007 |
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