Bioassay-Guided Isolation of Epiquinamide, a Novel Quinolizidine Alkaloid and Nicotinic Agonist from an Ecuadoran Poison Frog, Epipedobates tricolor
Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation and screening of a natural product extract. This method was used to guide the isolation of a novel quinolizidine alkaloid from the methanolic skin extracts of...
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| Veröffentlicht in: | Journal of natural products (Washington, D.C.) D.C.), 2003-10, Vol.66 (10), p.1345-1350 |
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| container_title | Journal of natural products (Washington, D.C.) |
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| creator | FITCH, Richard W. GARRAFFO, H. Martin SPANDE, Thomas F. YEH, Herman J. C. DALY, John W. |
| description | Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation and screening of a natural product extract. This method was used to guide the isolation of a novel quinolizidine alkaloid from the methanolic skin extracts of an Ecuadoran frog, Epipedobates tricolor. The structure was determined on the basis of MS, IR, and NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named this compound epiquinamide, reflecting its origin and structure. The activity of the isolated compound was determined in five cell lines expressing various nicotinic acetylcholine receptor subtypes. The bioactivity of epiquinamide was evaluated on the basis of membrane potential fluorescence and was found to be beta2 selective. This compound represents a new structural class of nicotinic agonists and a potential lead compound for the development of new therapeutics and pharmacological probes for nicotinic receptors. The off-line screening technique was found to be very sensitive for the detection of compounds active at nicotinic receptors. |
| doi_str_mv | 10.1021/np030306u |
| format | Article |
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The bioactivity of epiquinamide was evaluated on the basis of membrane potential fluorescence and was found to be beta2 selective. This compound represents a new structural class of nicotinic agonists and a potential lead compound for the development of new therapeutics and pharmacological probes for nicotinic receptors. The off-line screening technique was found to be very sensitive for the detection of compounds active at nicotinic receptors.</description><identifier>ISSN: 0163-3864</identifier><identifier>EISSN: 1520-6025</identifier><identifier>DOI: 10.1021/np030306u</identifier><identifier>PMID: 14575435</identifier><identifier>CODEN: JNPRDF</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Alkaloids - chemistry ; Alkaloids - isolation & purification ; Alkaloids - pharmacology ; Animal poisons toxicology. Antivenoms ; Animals ; Anura ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Ecuador ; Epipedobates tricolor ; Freshwater ; General pharmacology ; Medical sciences ; Molecular Structure ; Nicotinic Agonists - chemistry ; Nicotinic Agonists - isolation & purification ; Nicotinic Agonists - pharmacology ; Nuclear Magnetic Resonance, Biomolecular ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Quinolizines - chemistry ; Quinolizines - isolation & purification ; Quinolizines - pharmacology ; Ranidae - metabolism ; Receptors, Nicotinic - metabolism ; Skin - secretion ; Toxicology</subject><ispartof>Journal of natural products (Washington, D.C.), 2003-10, Vol.66 (10), p.1345-1350</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15235822$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14575435$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FITCH, Richard W.</creatorcontrib><creatorcontrib>GARRAFFO, H. Martin</creatorcontrib><creatorcontrib>SPANDE, Thomas F.</creatorcontrib><creatorcontrib>YEH, Herman J. C.</creatorcontrib><creatorcontrib>DALY, John W.</creatorcontrib><title>Bioassay-Guided Isolation of Epiquinamide, a Novel Quinolizidine Alkaloid and Nicotinic Agonist from an Ecuadoran Poison Frog, Epipedobates tricolor</title><title>Journal of natural products (Washington, D.C.)</title><addtitle>J. Nat. Prod</addtitle><description>Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation and screening of a natural product extract. This method was used to guide the isolation of a novel quinolizidine alkaloid from the methanolic skin extracts of an Ecuadoran frog, Epipedobates tricolor. The structure was determined on the basis of MS, IR, and NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named this compound epiquinamide, reflecting its origin and structure. The activity of the isolated compound was determined in five cell lines expressing various nicotinic acetylcholine receptor subtypes. The bioactivity of epiquinamide was evaluated on the basis of membrane potential fluorescence and was found to be beta2 selective. This compound represents a new structural class of nicotinic agonists and a potential lead compound for the development of new therapeutics and pharmacological probes for nicotinic receptors. The off-line screening technique was found to be very sensitive for the detection of compounds active at nicotinic receptors.</description><subject>Alkaloids - chemistry</subject><subject>Alkaloids - isolation & purification</subject><subject>Alkaloids - pharmacology</subject><subject>Animal poisons toxicology. Antivenoms</subject><subject>Animals</subject><subject>Anura</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Ecuador</subject><subject>Epipedobates tricolor</subject><subject>Freshwater</subject><subject>General pharmacology</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>Nicotinic Agonists - chemistry</subject><subject>Nicotinic Agonists - isolation & purification</subject><subject>Nicotinic Agonists - pharmacology</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinolizines - chemistry</subject><subject>Quinolizines - isolation & purification</subject><subject>Quinolizines - pharmacology</subject><subject>Ranidae - metabolism</subject><subject>Receptors, Nicotinic - metabolism</subject><subject>Skin - secretion</subject><subject>Toxicology</subject><issn>0163-3864</issn><issn>1520-6025</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMFu1DAQhi0EokvhwAsgX-DUgB3HjnPclm0pqpYCi8QtmtiTytSJUztBbZ-DB8aoC2gOM5r_m380Q8hLzt5yVvJ348REDrU8IisuS1YoVsrHZMW4EoXQqjogz1L6wViGGvmUHPBK1rISckV-HbsAKcFdcbY4i5aep-BhdmGkoaebyd0sboQhS0cU6Db8RE8_51bw7t5ZNyJd-2vwwVkKo6VbZ8LsRmfo-iqMLs20j2HIEt2YBWyIuboMLmX70xiujv5smNCGDmZMdI553If4nDzpwSd8sc-H5NvpZnfyobj4dHZ-sr4oXD52LkxlVMWbznLdK-R9U9tOG4YGGtNBI1WlOsCyBzRa9VygqIRCITvNdK00ikPy5sF3iuFmwTS3g0sGvYcRw5JaXteMM84z-GoPLt2Atp2iGyDetX__mIHXewCSAd_nO41L_zlZCqnLMnPFA5dfg7f_dIjXrapFLdvd5ddW1-93-uP3bftF_AbvmJLO</recordid><startdate>20031001</startdate><enddate>20031001</enddate><creator>FITCH, Richard W.</creator><creator>GARRAFFO, H. Martin</creator><creator>SPANDE, Thomas F.</creator><creator>YEH, Herman J. C.</creator><creator>DALY, John W.</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>F1W</scope><scope>H95</scope><scope>L.G</scope></search><sort><creationdate>20031001</creationdate><title>Bioassay-Guided Isolation of Epiquinamide, a Novel Quinolizidine Alkaloid and Nicotinic Agonist from an Ecuadoran Poison Frog, Epipedobates tricolor</title><author>FITCH, Richard W. ; GARRAFFO, H. Martin ; SPANDE, Thomas F. ; YEH, Herman J. 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Antivenoms</topic><topic>Animals</topic><topic>Anura</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Ecuador</topic><topic>Epipedobates tricolor</topic><topic>Freshwater</topic><topic>General pharmacology</topic><topic>Medical sciences</topic><topic>Molecular Structure</topic><topic>Nicotinic Agonists - chemistry</topic><topic>Nicotinic Agonists - isolation & purification</topic><topic>Nicotinic Agonists - pharmacology</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Pharmacognosy. Homeopathy. Health food</topic><topic>Pharmacology. Drug treatments</topic><topic>Quinolizines - chemistry</topic><topic>Quinolizines - isolation & purification</topic><topic>Quinolizines - pharmacology</topic><topic>Ranidae - metabolism</topic><topic>Receptors, Nicotinic - metabolism</topic><topic>Skin - secretion</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FITCH, Richard W.</creatorcontrib><creatorcontrib>GARRAFFO, H. Martin</creatorcontrib><creatorcontrib>SPANDE, Thomas F.</creatorcontrib><creatorcontrib>YEH, Herman J. C.</creatorcontrib><creatorcontrib>DALY, John W.</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>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Journal of natural products (Washington, D.C.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FITCH, Richard W.</au><au>GARRAFFO, H. Martin</au><au>SPANDE, Thomas F.</au><au>YEH, Herman J. C.</au><au>DALY, John W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bioassay-Guided Isolation of Epiquinamide, a Novel Quinolizidine Alkaloid and Nicotinic Agonist from an Ecuadoran Poison Frog, Epipedobates tricolor</atitle><jtitle>Journal of natural products (Washington, D.C.)</jtitle><addtitle>J. Nat. Prod</addtitle><date>2003-10-01</date><risdate>2003</risdate><volume>66</volume><issue>10</issue><spage>1345</spage><epage>1350</epage><pages>1345-1350</pages><issn>0163-3864</issn><eissn>1520-6025</eissn><coden>JNPRDF</coden><abstract>Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation and screening of a natural product extract. This method was used to guide the isolation of a novel quinolizidine alkaloid from the methanolic skin extracts of an Ecuadoran frog, Epipedobates tricolor. The structure was determined on the basis of MS, IR, and NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named this compound epiquinamide, reflecting its origin and structure. The activity of the isolated compound was determined in five cell lines expressing various nicotinic acetylcholine receptor subtypes. The bioactivity of epiquinamide was evaluated on the basis of membrane potential fluorescence and was found to be beta2 selective. This compound represents a new structural class of nicotinic agonists and a potential lead compound for the development of new therapeutics and pharmacological probes for nicotinic receptors. The off-line screening technique was found to be very sensitive for the detection of compounds active at nicotinic receptors.</abstract><cop>Washington, DC</cop><cop>Glendale, AZ</cop><pub>American Chemical Society</pub><pmid>14575435</pmid><doi>10.1021/np030306u</doi><tpages>6</tpages></addata></record> |
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| subjects | Alkaloids - chemistry Alkaloids - isolation & purification Alkaloids - pharmacology Animal poisons toxicology. Antivenoms Animals Anura Biological and medical sciences Chromatography, High Pressure Liquid Ecuador Epipedobates tricolor Freshwater General pharmacology Medical sciences Molecular Structure Nicotinic Agonists - chemistry Nicotinic Agonists - isolation & purification Nicotinic Agonists - pharmacology Nuclear Magnetic Resonance, Biomolecular Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments Quinolizines - chemistry Quinolizines - isolation & purification Quinolizines - pharmacology Ranidae - metabolism Receptors, Nicotinic - metabolism Skin - secretion Toxicology |
| title | Bioassay-Guided Isolation of Epiquinamide, a Novel Quinolizidine Alkaloid and Nicotinic Agonist from an Ecuadoran Poison Frog, Epipedobates tricolor |
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