Alantrypinone and its derivatives: Synthesis and antagonist activity toward insect GABA receptors
The γ-aminobutyric acid (GABA) receptor bears important sites of action for insecticides. Alantrypinone is an insecticidal alkaloid that acts as a selective antagonist for housefly (vs rat) GABA receptors, and is considered to be a lead compound for the development of a safer insecticide. In an atte...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2009, Vol.17 (1), p.94-110 |
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| creator | Watanabe, Takayuki Arisawa, Mitsuhiro Narusuye, Kenji Alam, Mohommad Sayed Yamamoto, Kazumi Mitomi, Masaaki Ozoe, Yoshihisa Nishida, Atsushi |
| description | The γ-aminobutyric acid (GABA) receptor bears important sites of action for insecticides. Alantrypinone is an insecticidal alkaloid that acts as a selective antagonist for housefly (vs rat) GABA receptors, and is considered to be a lead compound for the development of a safer insecticide. In an attempt to obtain compounds with greater activity, a series of racemic alantrypinone derivatives were systematically synthesized using hetero Diels–Alder reactions, and a total of 34 compounds were examined for their ability to inhibit the specific binding of [
3H]4′-ethynyl-4-
n-propylbicycloorthobenzoate, a high-affinity non-competitive antagonist, to housefly-head membranes. The assay results showed that (1) there is no significant difference between the potencies of natural (+)-alantrypinone and its synthetic racemate; (2) the amide NHs at the 2- and 18-positions are important for high activity; (3) there is a considerable drop in potency for compounds without an aromatic ring at the 16-position; and (4) a large substituent at the 3-position is detrimental to high activity. |
| doi_str_mv | 10.1016/j.bmc.2008.11.017 |
| format | Article |
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3H]4′-ethynyl-4-
n-propylbicycloorthobenzoate, a high-affinity non-competitive antagonist, to housefly-head membranes. The assay results showed that (1) there is no significant difference between the potencies of natural (+)-alantrypinone and its synthetic racemate; (2) the amide NHs at the 2- and 18-positions are important for high activity; (3) there is a considerable drop in potency for compounds without an aromatic ring at the 16-position; and (4) a large substituent at the 3-position is detrimental to high activity.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2008.11.017</identifier><identifier>PMID: 19062297</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Alantrypinone ; Alkaloids - chemical synthesis ; Alkaloids - pharmacology ; Animals ; Binding, Competitive ; Biological and medical sciences ; Chemical control ; Control ; Fundamental and applied biological sciences. Psychology ; GABA Antagonists - chemical synthesis ; Hetero Diels–Alder reaction ; Houseflies ; Indoles - chemical synthesis ; Indoles - pharmacology ; Insect GABA receptors ; Insecticides - chemical synthesis ; Insecticides - pharmacology ; Phytopathology. Animal pests. Plant and forest protection ; Protozoa. Invertebrates ; Quinazolines - chemical synthesis ; Quinazolines - pharmacology ; Rats ; Receptors, GABA - drug effects ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry, 2009, Vol.17 (1), p.94-110</ispartof><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-8dffc1c9fa1b83ec1ea2a9009ae689b441b14ebfeb9efc5c9dbc992723586b223</citedby><cites>FETCH-LOGICAL-c443t-8dffc1c9fa1b83ec1ea2a9009ae689b441b14ebfeb9efc5c9dbc992723586b223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089608010845$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,4010,27902,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21010941$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19062297$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watanabe, Takayuki</creatorcontrib><creatorcontrib>Arisawa, Mitsuhiro</creatorcontrib><creatorcontrib>Narusuye, Kenji</creatorcontrib><creatorcontrib>Alam, Mohommad Sayed</creatorcontrib><creatorcontrib>Yamamoto, Kazumi</creatorcontrib><creatorcontrib>Mitomi, Masaaki</creatorcontrib><creatorcontrib>Ozoe, Yoshihisa</creatorcontrib><creatorcontrib>Nishida, Atsushi</creatorcontrib><title>Alantrypinone and its derivatives: Synthesis and antagonist activity toward insect GABA receptors</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>The γ-aminobutyric acid (GABA) receptor bears important sites of action for insecticides. Alantrypinone is an insecticidal alkaloid that acts as a selective antagonist for housefly (vs rat) GABA receptors, and is considered to be a lead compound for the development of a safer insecticide. In an attempt to obtain compounds with greater activity, a series of racemic alantrypinone derivatives were systematically synthesized using hetero Diels–Alder reactions, and a total of 34 compounds were examined for their ability to inhibit the specific binding of [
3H]4′-ethynyl-4-
n-propylbicycloorthobenzoate, a high-affinity non-competitive antagonist, to housefly-head membranes. The assay results showed that (1) there is no significant difference between the potencies of natural (+)-alantrypinone and its synthetic racemate; (2) the amide NHs at the 2- and 18-positions are important for high activity; (3) there is a considerable drop in potency for compounds without an aromatic ring at the 16-position; and (4) a large substituent at the 3-position is detrimental to high activity.</description><subject>Alantrypinone</subject><subject>Alkaloids - chemical synthesis</subject><subject>Alkaloids - pharmacology</subject><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>Chemical control</subject><subject>Control</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>GABA Antagonists - chemical synthesis</subject><subject>Hetero Diels–Alder reaction</subject><subject>Houseflies</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - pharmacology</subject><subject>Insect GABA receptors</subject><subject>Insecticides - chemical synthesis</subject><subject>Insecticides - pharmacology</subject><subject>Phytopathology. Animal pests. Plant and forest protection</subject><subject>Protozoa. Invertebrates</subject><subject>Quinazolines - chemical synthesis</subject><subject>Quinazolines - pharmacology</subject><subject>Rats</subject><subject>Receptors, GABA - drug effects</subject><subject>Structure-Activity Relationship</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFPGzEQhS1UVFLaH8AF7aXcdvF4HWdNTwEVioTUQ9uzZXtnW0eJN3icoPx7TBPBreppDvO9p5n3GDsD3gAHdblo3Mo3gvOuAWg4zI7YBKSSddtqeMcmXKuu5p1WJ-wD0YJzLqSG9-wENFdC6NmE2fnSxpx26xDHiJWNfRUyVT2msLU5bJGuqh-7mP8gBfq7Lrj9PcZAubK-ECHvqjw-2VSUkdDn6m5-Pa8SelznMdFHdjzYJeGnwzxlv26__rz5Vj98v7u_mT_UXso2110_DB68Hiy4rkUPaIXVnGuLqtNOSnAg0Q3oNA5-6nXvvNZiJtppp5wQ7Sm72Puu0_i4QcpmFcjjsvyH44ZMiUnx6Yz_DwhTJdsCwh70aSRKOJh1Ciubdga4eSnALEwp4EXQGQBTCiia84P5xq2wf1McEi_A5wNgydvlkGz0gV45UXy5llC4L3sOS2bbgMmQDxg99qFEm00_hn-c8QxWhqTJ</recordid><startdate>2009</startdate><enddate>2009</enddate><creator>Watanabe, Takayuki</creator><creator>Arisawa, Mitsuhiro</creator><creator>Narusuye, Kenji</creator><creator>Alam, Mohommad Sayed</creator><creator>Yamamoto, Kazumi</creator><creator>Mitomi, Masaaki</creator><creator>Ozoe, Yoshihisa</creator><creator>Nishida, Atsushi</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>7QO</scope><scope>7SS</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>2009</creationdate><title>Alantrypinone and its derivatives: Synthesis and antagonist activity toward insect GABA receptors</title><author>Watanabe, Takayuki ; Arisawa, Mitsuhiro ; Narusuye, Kenji ; Alam, Mohommad Sayed ; Yamamoto, Kazumi ; Mitomi, Masaaki ; Ozoe, Yoshihisa ; Nishida, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-8dffc1c9fa1b83ec1ea2a9009ae689b441b14ebfeb9efc5c9dbc992723586b223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alantrypinone</topic><topic>Alkaloids - chemical synthesis</topic><topic>Alkaloids - pharmacology</topic><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>Chemical control</topic><topic>Control</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>GABA Antagonists - chemical synthesis</topic><topic>Hetero Diels–Alder reaction</topic><topic>Houseflies</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - pharmacology</topic><topic>Insect GABA receptors</topic><topic>Insecticides - chemical synthesis</topic><topic>Insecticides - pharmacology</topic><topic>Phytopathology. Animal pests. Plant and forest protection</topic><topic>Protozoa. Invertebrates</topic><topic>Quinazolines - chemical synthesis</topic><topic>Quinazolines - pharmacology</topic><topic>Rats</topic><topic>Receptors, GABA - drug effects</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watanabe, Takayuki</creatorcontrib><creatorcontrib>Arisawa, Mitsuhiro</creatorcontrib><creatorcontrib>Narusuye, Kenji</creatorcontrib><creatorcontrib>Alam, Mohommad Sayed</creatorcontrib><creatorcontrib>Yamamoto, Kazumi</creatorcontrib><creatorcontrib>Mitomi, Masaaki</creatorcontrib><creatorcontrib>Ozoe, Yoshihisa</creatorcontrib><creatorcontrib>Nishida, Atsushi</creatorcontrib><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>Biotechnology Research Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watanabe, Takayuki</au><au>Arisawa, Mitsuhiro</au><au>Narusuye, Kenji</au><au>Alam, Mohommad Sayed</au><au>Yamamoto, Kazumi</au><au>Mitomi, Masaaki</au><au>Ozoe, Yoshihisa</au><au>Nishida, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alantrypinone and its derivatives: Synthesis and antagonist activity toward insect GABA receptors</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2009</date><risdate>2009</risdate><volume>17</volume><issue>1</issue><spage>94</spage><epage>110</epage><pages>94-110</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>The γ-aminobutyric acid (GABA) receptor bears important sites of action for insecticides. Alantrypinone is an insecticidal alkaloid that acts as a selective antagonist for housefly (vs rat) GABA receptors, and is considered to be a lead compound for the development of a safer insecticide. In an attempt to obtain compounds with greater activity, a series of racemic alantrypinone derivatives were systematically synthesized using hetero Diels–Alder reactions, and a total of 34 compounds were examined for their ability to inhibit the specific binding of [
3H]4′-ethynyl-4-
n-propylbicycloorthobenzoate, a high-affinity non-competitive antagonist, to housefly-head membranes. The assay results showed that (1) there is no significant difference between the potencies of natural (+)-alantrypinone and its synthetic racemate; (2) the amide NHs at the 2- and 18-positions are important for high activity; (3) there is a considerable drop in potency for compounds without an aromatic ring at the 16-position; and (4) a large substituent at the 3-position is detrimental to high activity.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19062297</pmid><doi>10.1016/j.bmc.2008.11.017</doi><tpages>17</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Alantrypinone Alkaloids - chemical synthesis Alkaloids - pharmacology Animals Binding, Competitive Biological and medical sciences Chemical control Control Fundamental and applied biological sciences. Psychology GABA Antagonists - chemical synthesis Hetero Diels–Alder reaction Houseflies Indoles - chemical synthesis Indoles - pharmacology Insect GABA receptors Insecticides - chemical synthesis Insecticides - pharmacology Phytopathology. Animal pests. Plant and forest protection Protozoa. Invertebrates Quinazolines - chemical synthesis Quinazolines - pharmacology Rats Receptors, GABA - drug effects Structure-Activity Relationship |
| title | Alantrypinone and its derivatives: Synthesis and antagonist activity toward insect GABA receptors |
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