Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones
The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions betwe...
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| Veröffentlicht in: | Journal of medicinal chemistry 1992-06, Vol.35 (13), p.2452-2458 |
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| container_end_page | 2458 |
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| container_issue | 13 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 35 |
| creator | Giordano, Oscar S Pestchanker, Mauricio J Guerreiro, Eduardo Saad, Jose R Enriz, Ricardo D Rodriguez, Ana M Jauregui, Esteban A Guzman, Jorge Maria, Alejandra O. M Wendel, Graciela H |
| description | The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins. |
| doi_str_mv | 10.1021/jm00091a013 |
| format | Article |
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M ; Wendel, Graciela H</creator><creatorcontrib>Giordano, Oscar S ; Pestchanker, Mauricio J ; Guerreiro, Eduardo ; Saad, Jose R ; Enriz, Ricardo D ; Rodriguez, Ana M ; Jauregui, Esteban A ; Guzman, Jorge ; Maria, Alejandra O. M ; Wendel, Graciela H</creatorcontrib><description>The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00091a013</identifier><identifier>PMID: 1619619</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Alicyclic compounds, terpenoids, prostaglandins, steroids ; Chemistry ; Exact sciences and technology ; Lactones - pharmacology ; Molecular Conformation ; Organic chemistry ; Preparations and properties ; Sesquiterpenes - pharmacology ; Stomach - drug effects ; Structure-Activity Relationship ; Terpenoids</subject><ispartof>Journal of medicinal chemistry, 1992-06, Vol.35 (13), p.2452-2458</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a383t-2e423fd6dc3014081c4d25ec90cd866bdadbe80413acee2df6b5da62b8eb921a3</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/jm00091a013$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00091a013$$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=5407075$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1619619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giordano, Oscar S</creatorcontrib><creatorcontrib>Pestchanker, Mauricio J</creatorcontrib><creatorcontrib>Guerreiro, Eduardo</creatorcontrib><creatorcontrib>Saad, Jose R</creatorcontrib><creatorcontrib>Enriz, Ricardo D</creatorcontrib><creatorcontrib>Rodriguez, Ana M</creatorcontrib><creatorcontrib>Jauregui, Esteban A</creatorcontrib><creatorcontrib>Guzman, Jorge</creatorcontrib><creatorcontrib>Maria, Alejandra O. M</creatorcontrib><creatorcontrib>Wendel, Graciela H</creatorcontrib><title>Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.</description><subject>Alicyclic compounds, terpenoids, prostaglandins, steroids</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Lactones - pharmacology</subject><subject>Molecular Conformation</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Stomach - drug effects</subject><subject>Structure-Activity Relationship</subject><subject>Terpenoids</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1r3DAQhkVJSLdpTz0XdAjNoTjVhy17j2WTtIGQFnbbqxhLo0Ybr72R5JD991XwkuYQEIzgfXiZeQj5yNkZZ4J_XW8YY3MOjMs3ZMYrwYqyYeUBmTEmRCGUkG_JuxjXGZNcyCNyxBWf5zcjbpnCaNIYsACT_INPOxqwg-SHPt76LfU9TbdI_0JMwRtqdmnYhiHhE4wUncs_Ojga8QEDdHnG-9EnDFvskXa5dOgxvieHDrqIH_bzmPy-vFgtfhTXP79fLb5dFyAbmQqBpZDOKmsk4yVruCmtqNDMmbGNUq0F22I-jUswiMI61VYWlGgbbOeCgzwmn6fevOP9iDHpjY8Guw56HMaoa5kNsKbO4JcJNGGIMaDT2-A3EHaaM_1kVb-wmulP-9qx3aD9z04ac36yzyEa6FyA3vj4jFUlq1ldZayYMB8TPj7HEO60qmVd6dWvpT5fnF-u_qilvsn86cSDiXo9jKHP7l5d8B8r2Z2_</recordid><startdate>19920601</startdate><enddate>19920601</enddate><creator>Giordano, Oscar S</creator><creator>Pestchanker, Mauricio J</creator><creator>Guerreiro, Eduardo</creator><creator>Saad, Jose R</creator><creator>Enriz, Ricardo D</creator><creator>Rodriguez, Ana M</creator><creator>Jauregui, Esteban A</creator><creator>Guzman, Jorge</creator><creator>Maria, Alejandra O. 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M</au><au>Wendel, Graciela H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1992-06-01</date><risdate>1992</risdate><volume>35</volume><issue>13</issue><spage>2452</spage><epage>2458</epage><pages>2452-2458</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>1619619</pmid><doi>10.1021/jm00091a013</doi><tpages>7</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1992-06, Vol.35 (13), p.2452-2458 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Alicyclic compounds, terpenoids, prostaglandins, steroids Chemistry Exact sciences and technology Lactones - pharmacology Molecular Conformation Organic chemistry Preparations and properties Sesquiterpenes - pharmacology Stomach - drug effects Structure-Activity Relationship Terpenoids |
| title | Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones |
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