Microbial Transformation of L-696, 474, a Novel Cytochalasin as an Inhibitor of HIV-1 Protease
The microbiological transformation of L-696,474 [1], a novel cytochalasin that is an inhibitor of HIV-1 protease, was investigated using Actinoplanes sp. ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have und...
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| Veröffentlicht in: | Journal of natural products (Washington, D.C.) D.C.), 1993-05, Vol.56 (5), p.755-761 |
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| container_issue | 5 |
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| container_title | Journal of natural products (Washington, D.C.) |
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| creator | Chen, Tom S Doss, George A Hsu, Annjia Hsu, Amy Lingham, Russell B White, Raymond F Monaghan, Richard L |
| description | The microbiological transformation of L-696,474 [1], a novel cytochalasin that is an inhibitor of HIV-1 protease, was investigated using Actinoplanes sp. ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C-16 methyl group (C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxylated at the para (C-29), the meta (C-28), and both the para and the meta, positions of the phenyl ring, respectively. Metabolites 6 and 7 were shown to result from vicinal dihydroxylation on both C-16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the meta position of the phenyl ring. The structures of the metabolites were established using spectroscopic techniques including ms, 1H nmr, 13C nmr, and various 2D nmr spectroscopy experiments. |
| doi_str_mv | 10.1021/np50095a013 |
| format | Article |
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ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C-16 methyl group (C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxylated at the para (C-29), the meta (C-28), and both the para and the meta, positions of the phenyl ring, respectively. Metabolites 6 and 7 were shown to result from vicinal dihydroxylation on both C-16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the meta position of the phenyl ring. The structures of the metabolites were established using spectroscopic techniques including ms, 1H nmr, 13C nmr, and various 2D nmr spectroscopy experiments.</description><identifier>ISSN: 0163-3864</identifier><identifier>EISSN: 1520-6025</identifier><identifier>DOI: 10.1021/np50095a013</identifier><identifier>PMID: 8326323</identifier><identifier>CODEN: JNPRDF</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Actinomycetales - metabolism ; AIDS/HIV ; Amino Acid Sequence ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Biological and medical sciences ; Biotransformation ; Cytochalasins - metabolism ; HIV Protease Inhibitors - metabolism ; Hydroxylation ; Isoindoles ; Medical sciences ; Molecular Sequence Data ; Pharmacology. Drug treatments</subject><ispartof>Journal of natural products (Washington, D.C.), 1993-05, Vol.56 (5), p.755-761</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a449t-8309985ce00af9e510aeed94adc8111240b7dd3045173b70c3b55b188aeb031f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/np50095a013$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/np50095a013$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4736479$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8326323$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Tom S</creatorcontrib><creatorcontrib>Doss, George A</creatorcontrib><creatorcontrib>Hsu, Annjia</creatorcontrib><creatorcontrib>Hsu, Amy</creatorcontrib><creatorcontrib>Lingham, Russell B</creatorcontrib><creatorcontrib>White, Raymond F</creatorcontrib><creatorcontrib>Monaghan, Richard L</creatorcontrib><title>Microbial Transformation of L-696, 474, a Novel Cytochalasin as an Inhibitor of HIV-1 Protease</title><title>Journal of natural products (Washington, D.C.)</title><addtitle>J. Nat. Prod</addtitle><description>The microbiological transformation of L-696,474 [1], a novel cytochalasin that is an inhibitor of HIV-1 protease, was investigated using Actinoplanes sp. ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C-16 methyl group (C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxylated at the para (C-29), the meta (C-28), and both the para and the meta, positions of the phenyl ring, respectively. Metabolites 6 and 7 were shown to result from vicinal dihydroxylation on both C-16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the meta position of the phenyl ring. The structures of the metabolites were established using spectroscopic techniques including ms, 1H nmr, 13C nmr, and various 2D nmr spectroscopy experiments.</description><subject>Actinomycetales - metabolism</subject><subject>AIDS/HIV</subject><subject>Amino Acid Sequence</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>Cytochalasins - metabolism</subject><subject>HIV Protease Inhibitors - metabolism</subject><subject>Hydroxylation</subject><subject>Isoindoles</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Pharmacology. Drug treatments</subject><issn>0163-3864</issn><issn>1520-6025</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0M9v0zAUB3ALMY0yOHFG8gGNAwt7jn8lRxQNVqmMSut2xHpxHM0jjYudTuy_n6dWFYedfPh-3tPzl5APDL4yKNn5uJEAtURg_BWZMVlCoaCUr8kMmOIFr5R4Q96mdA8APMNjclzxUvGSz8jvn97G0Hoc6CrimPoQ1zj5MNLQ00WhanVGhRZnFOlVeHADbR6nYO9wwORHioniSOfjnW_9FOLzzOX8tmB0GcPkMLl35KjHIbn3-_eE3Hy_WDWXxeLXj3nzbVGgEPVUVPmsupLWAWBfO8kAnetqgZ2tGGOlgFZ3HQchmeatBstbKVtWVeha4KznJ-R0t3cTw9-tS5NZ-2TdMODowjYZLStVs1Jm-GUH869Tiq43m-jXGB8NA_Pcpvmvzaw_7tdu27XrDnZfX84_7XNMFoc-N2h9OjChuRK6zqzYMZ8m9-8QY_xjlOZamtXy2jS3iyt9vWyMyv7zzqNN5j5s45i7e_HAJ5XplLE</recordid><startdate>19930501</startdate><enddate>19930501</enddate><creator>Chen, Tom S</creator><creator>Doss, George A</creator><creator>Hsu, Annjia</creator><creator>Hsu, Amy</creator><creator>Lingham, Russell B</creator><creator>White, Raymond F</creator><creator>Monaghan, Richard L</creator><general>American Chemical Society</general><general>American Society of Pharmacognosy</general><scope>BSCLL</scope><scope>IQODW</scope><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></search><sort><creationdate>19930501</creationdate><title>Microbial Transformation of L-696, 474, a Novel Cytochalasin as an Inhibitor of HIV-1 Protease</title><author>Chen, Tom S ; Doss, George A ; Hsu, Annjia ; Hsu, Amy ; Lingham, Russell B ; White, Raymond F ; Monaghan, Richard L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a449t-8309985ce00af9e510aeed94adc8111240b7dd3045173b70c3b55b188aeb031f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Actinomycetales - metabolism</topic><topic>AIDS/HIV</topic><topic>Amino Acid Sequence</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>Cytochalasins - metabolism</topic><topic>HIV Protease Inhibitors - metabolism</topic><topic>Hydroxylation</topic><topic>Isoindoles</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Pharmacology. Drug treatments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Tom S</creatorcontrib><creatorcontrib>Doss, George A</creatorcontrib><creatorcontrib>Hsu, Annjia</creatorcontrib><creatorcontrib>Hsu, Amy</creatorcontrib><creatorcontrib>Lingham, Russell B</creatorcontrib><creatorcontrib>White, Raymond F</creatorcontrib><creatorcontrib>Monaghan, Richard L</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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><jtitle>Journal of natural products (Washington, D.C.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Tom S</au><au>Doss, George A</au><au>Hsu, Annjia</au><au>Hsu, Amy</au><au>Lingham, Russell B</au><au>White, Raymond F</au><au>Monaghan, Richard L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microbial Transformation of L-696, 474, a Novel Cytochalasin as an Inhibitor of HIV-1 Protease</atitle><jtitle>Journal of natural products (Washington, D.C.)</jtitle><addtitle>J. Nat. Prod</addtitle><date>1993-05-01</date><risdate>1993</risdate><volume>56</volume><issue>5</issue><spage>755</spage><epage>761</epage><pages>755-761</pages><issn>0163-3864</issn><eissn>1520-6025</eissn><coden>JNPRDF</coden><abstract>The microbiological transformation of L-696,474 [1], a novel cytochalasin that is an inhibitor of HIV-1 protease, was investigated using Actinoplanes sp. ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C-16 methyl group (C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxylated at the para (C-29), the meta (C-28), and both the para and the meta, positions of the phenyl ring, respectively. Metabolites 6 and 7 were shown to result from vicinal dihydroxylation on both C-16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the meta position of the phenyl ring. The structures of the metabolites were established using spectroscopic techniques including ms, 1H nmr, 13C nmr, and various 2D nmr spectroscopy experiments.</abstract><cop>Washington, DC</cop><cop>Glendale, AZ</cop><pub>American Chemical Society</pub><pmid>8326323</pmid><doi>10.1021/np50095a013</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 0163-3864 |
| ispartof | Journal of natural products (Washington, D.C.), 1993-05, Vol.56 (5), p.755-761 |
| issn | 0163-3864 1520-6025 |
| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Actinomycetales - metabolism AIDS/HIV Amino Acid Sequence Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Biotransformation Cytochalasins - metabolism HIV Protease Inhibitors - metabolism Hydroxylation Isoindoles Medical sciences Molecular Sequence Data Pharmacology. Drug treatments |
| title | Microbial Transformation of L-696, 474, a Novel Cytochalasin as an Inhibitor of HIV-1 Protease |
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