Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists
A new CoMFA model of baogongteng A (BGT-A) and its derivatives with agonistic activity to muscarinic receptors was constructed, discussed, and examined. This model could provide solid basis for designing novel molecules with higher agonistic activity to muscarinic receptors. Baogongteng A (BGT-A), a...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2005-11, Vol.15 (21), p.4814-4818 |
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| creator | Niu, Yin-Yao Yang, Li-Min Liu, Hui-Zhong Cui, Yong-Yao Zhu, Liang Feng, Ju-Mei Yao, Jian-Hua Chen, Hong-Zhuan Fan, Bo-Tao Chen, Ze-Nai Lu, Yang |
| description | A new CoMFA model of baogongteng A (BGT-A) and its derivatives with agonistic activity to muscarinic receptors was constructed, discussed, and examined. This model could provide solid basis for designing novel molecules with higher agonistic activity to muscarinic receptors.
Baogongteng A (BGT-A), a naturally occurring tropane muscarinic agonist isolated from Chinese medicinal plant, exhibits a bioactive effect different from those of many tropane alkaloids that are muscarinic antagonists. A series of racemic derivatives of BGT-A was synthesized to study the structure–activity relationships (SAR). To explore further the SAR in this series and to ultimately design muscarinic agonists for drug development, a Comparative Molecular Field Analysis (CoMFA) was performed. The values of the leave-one-out cross-validated correlation coefficient
q
2 and the conventional correlation coefficient
r
2 for the model are 0.613 and 0.965, respectively. The regression analysis of the data indicated that the steric effect of N-substituted group on tropane of analyzed compounds critically affected the agonistic activity to muscarinic receptors. |
| doi_str_mv | 10.1016/j.bmcl.2005.07.045 |
| format | Article |
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Baogongteng A (BGT-A), a naturally occurring tropane muscarinic agonist isolated from Chinese medicinal plant, exhibits a bioactive effect different from those of many tropane alkaloids that are muscarinic antagonists. A series of racemic derivatives of BGT-A was synthesized to study the structure–activity relationships (SAR). To explore further the SAR in this series and to ultimately design muscarinic agonists for drug development, a Comparative Molecular Field Analysis (CoMFA) was performed. The values of the leave-one-out cross-validated correlation coefficient
q
2 and the conventional correlation coefficient
r
2 for the model are 0.613 and 0.965, respectively. The regression analysis of the data indicated that the steric effect of N-substituted group on tropane of analyzed compounds critically affected the agonistic activity to muscarinic receptors.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2005.07.045</identifier><identifier>PMID: 16153841</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Agonistic ; Animals ; Baogongteng A ; Biological and medical sciences ; Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; Cholinergic system ; CoMFA ; Guinea Pigs ; Medical sciences ; Models, Molecular ; Muscarinic Agonists - chemical synthesis ; Muscarinic Agonists - pharmacology ; Muscarinic receptors ; Muscle, Skeletal - chemistry ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Plant Extracts ; Protein Binding ; Quantitative Structure-Activity Relationship ; Receptors, Muscarinic - chemistry ; Receptors, Muscarinic - metabolism ; Tropanes - chemical synthesis ; Tropanes - pharmacology</subject><ispartof>Bioorganic & medicinal chemistry letters, 2005-11, Vol.15 (21), p.4814-4818</ispartof><rights>2005 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-44a83f80b1b163ce067a600575690f6e8fcdeda488cda1488743acb7ca32b2383</citedby><cites>FETCH-LOGICAL-c384t-44a83f80b1b163ce067a600575690f6e8fcdeda488cda1488743acb7ca32b2383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X05009285$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17146755$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16153841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niu, Yin-Yao</creatorcontrib><creatorcontrib>Yang, Li-Min</creatorcontrib><creatorcontrib>Liu, Hui-Zhong</creatorcontrib><creatorcontrib>Cui, Yong-Yao</creatorcontrib><creatorcontrib>Zhu, Liang</creatorcontrib><creatorcontrib>Feng, Ju-Mei</creatorcontrib><creatorcontrib>Yao, Jian-Hua</creatorcontrib><creatorcontrib>Chen, Hong-Zhuan</creatorcontrib><creatorcontrib>Fan, Bo-Tao</creatorcontrib><creatorcontrib>Chen, Ze-Nai</creatorcontrib><creatorcontrib>Lu, Yang</creatorcontrib><title>Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>A new CoMFA model of baogongteng A (BGT-A) and its derivatives with agonistic activity to muscarinic receptors was constructed, discussed, and examined. This model could provide solid basis for designing novel molecules with higher agonistic activity to muscarinic receptors.
Baogongteng A (BGT-A), a naturally occurring tropane muscarinic agonist isolated from Chinese medicinal plant, exhibits a bioactive effect different from those of many tropane alkaloids that are muscarinic antagonists. A series of racemic derivatives of BGT-A was synthesized to study the structure–activity relationships (SAR). To explore further the SAR in this series and to ultimately design muscarinic agonists for drug development, a Comparative Molecular Field Analysis (CoMFA) was performed. The values of the leave-one-out cross-validated correlation coefficient
q
2 and the conventional correlation coefficient
r
2 for the model are 0.613 and 0.965, respectively. The regression analysis of the data indicated that the steric effect of N-substituted group on tropane of analyzed compounds critically affected the agonistic activity to muscarinic receptors.</description><subject>Agonistic</subject><subject>Animals</subject><subject>Baogongteng A</subject><subject>Biological and medical sciences</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</subject><subject>Cholinergic system</subject><subject>CoMFA</subject><subject>Guinea Pigs</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Muscarinic Agonists - chemical synthesis</subject><subject>Muscarinic Agonists - pharmacology</subject><subject>Muscarinic receptors</subject><subject>Muscle, Skeletal - chemistry</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Plant Extracts</subject><subject>Protein Binding</subject><subject>Quantitative Structure-Activity Relationship</subject><subject>Receptors, Muscarinic - chemistry</subject><subject>Receptors, Muscarinic - metabolism</subject><subject>Tropanes - chemical synthesis</subject><subject>Tropanes - pharmacology</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCH-CAfIFbwjhxHK_EZVXRglQJ0RaJm-XYk5VX-SgeZ6X993i7K_XGaQ5-3teex4x9EFAKEOrLruxGN5QVQFNCW4JsXrGVkEoWtYTmNVvBWkGh1_LPBbsk2gEICVK-ZRdCiabWUqzYw8alsA_pwO3k-a-HzT2ntPgDn3ve2Xk7T9uE05Zvns9DIu4xhr3NISRuiY8LORvDFBy3mQ6U6B1709uB8P15XrHfN98er78Xdz9vf1xv7gqX706FlFbXvYZOdELVDkG1VuVd2katoVeoe-fRW6m181bk0crauq51tq66qtb1Fft86n2K898FKZkxkMNhsBPOCxmlVVUpLTNYnUAXZ6KIvXmKYbTxYASYo0qzM0eV5qjSQGuyyhz6eG5fuhH9S-TsLgOfzoDNCoY-2skFeuHa_BVtcyz6euIwu9gHjIZcwMmhDxFdMn4O_3vHP5BAkbA</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>Niu, Yin-Yao</creator><creator>Yang, Li-Min</creator><creator>Liu, Hui-Zhong</creator><creator>Cui, Yong-Yao</creator><creator>Zhu, Liang</creator><creator>Feng, Ju-Mei</creator><creator>Yao, Jian-Hua</creator><creator>Chen, Hong-Zhuan</creator><creator>Fan, Bo-Tao</creator><creator>Chen, Ze-Nai</creator><creator>Lu, Yang</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>7X8</scope></search><sort><creationdate>20051101</creationdate><title>Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists</title><author>Niu, Yin-Yao ; Yang, Li-Min ; Liu, Hui-Zhong ; Cui, Yong-Yao ; Zhu, Liang ; Feng, Ju-Mei ; Yao, Jian-Hua ; Chen, Hong-Zhuan ; Fan, Bo-Tao ; Chen, Ze-Nai ; Lu, Yang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-44a83f80b1b163ce067a600575690f6e8fcdeda488cda1488743acb7ca32b2383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Agonistic</topic><topic>Animals</topic><topic>Baogongteng A</topic><topic>Biological and medical sciences</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</topic><topic>Cholinergic system</topic><topic>CoMFA</topic><topic>Guinea Pigs</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Muscarinic Agonists - chemical synthesis</topic><topic>Muscarinic Agonists - pharmacology</topic><topic>Muscarinic receptors</topic><topic>Muscle, Skeletal - chemistry</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Plant Extracts</topic><topic>Protein Binding</topic><topic>Quantitative Structure-Activity Relationship</topic><topic>Receptors, Muscarinic - chemistry</topic><topic>Receptors, Muscarinic - metabolism</topic><topic>Tropanes - chemical synthesis</topic><topic>Tropanes - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niu, Yin-Yao</creatorcontrib><creatorcontrib>Yang, Li-Min</creatorcontrib><creatorcontrib>Liu, Hui-Zhong</creatorcontrib><creatorcontrib>Cui, Yong-Yao</creatorcontrib><creatorcontrib>Zhu, Liang</creatorcontrib><creatorcontrib>Feng, Ju-Mei</creatorcontrib><creatorcontrib>Yao, Jian-Hua</creatorcontrib><creatorcontrib>Chen, Hong-Zhuan</creatorcontrib><creatorcontrib>Fan, Bo-Tao</creatorcontrib><creatorcontrib>Chen, Ze-Nai</creatorcontrib><creatorcontrib>Lu, Yang</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>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niu, Yin-Yao</au><au>Yang, Li-Min</au><au>Liu, Hui-Zhong</au><au>Cui, Yong-Yao</au><au>Zhu, Liang</au><au>Feng, Ju-Mei</au><au>Yao, Jian-Hua</au><au>Chen, Hong-Zhuan</au><au>Fan, Bo-Tao</au><au>Chen, Ze-Nai</au><au>Lu, Yang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>15</volume><issue>21</issue><spage>4814</spage><epage>4818</epage><pages>4814-4818</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>A new CoMFA model of baogongteng A (BGT-A) and its derivatives with agonistic activity to muscarinic receptors was constructed, discussed, and examined. This model could provide solid basis for designing novel molecules with higher agonistic activity to muscarinic receptors.
Baogongteng A (BGT-A), a naturally occurring tropane muscarinic agonist isolated from Chinese medicinal plant, exhibits a bioactive effect different from those of many tropane alkaloids that are muscarinic antagonists. A series of racemic derivatives of BGT-A was synthesized to study the structure–activity relationships (SAR). To explore further the SAR in this series and to ultimately design muscarinic agonists for drug development, a Comparative Molecular Field Analysis (CoMFA) was performed. The values of the leave-one-out cross-validated correlation coefficient
q
2 and the conventional correlation coefficient
r
2 for the model are 0.613 and 0.965, respectively. The regression analysis of the data indicated that the steric effect of N-substituted group on tropane of analyzed compounds critically affected the agonistic activity to muscarinic receptors.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>16153841</pmid><doi>10.1016/j.bmcl.2005.07.045</doi><tpages>5</tpages></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry letters, 2005-11, Vol.15 (21), p.4814-4818 |
| issn | 0960-894X 1464-3405 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Agonistic Animals Baogongteng A Biological and medical sciences Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cholinergic system CoMFA Guinea Pigs Medical sciences Models, Molecular Muscarinic Agonists - chemical synthesis Muscarinic Agonists - pharmacology Muscarinic receptors Muscle, Skeletal - chemistry Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Plant Extracts Protein Binding Quantitative Structure-Activity Relationship Receptors, Muscarinic - chemistry Receptors, Muscarinic - metabolism Tropanes - chemical synthesis Tropanes - pharmacology |
| title | Activity and QSAR study of baogongteng A and its derivatives as muscarinic agonists |
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