Enhancement of antiproliferative activity by molecular simplification of catalpol
Molecular simplification of any given natural or synthetic template helps medicinal chemists designing shorten synthetic routes while keeping or enhancing the biological activity. This strategy is exemplified with simplified analogs of naturally occurring catalpol. Two iridoid scaffolds were synthes...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2010-04, Vol.18 (7), p.2515-2523 |
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| creator | García, Celina León, Leticia G. Pungitore, Carlos R. Ríos-Luci, Carla Daranas, Antonio H. Montero, Juan C. Pandiella, Atanasio Tonn, Carlos E. Martín, Víctor S. Padrón, José M. |
| description | Molecular simplification of any given natural or synthetic template helps medicinal chemists designing shorten synthetic routes while keeping or enhancing the biological activity. This strategy is exemplified with simplified analogs of naturally occurring catalpol.
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed α-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38–1.86μM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G1 phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining. |
| doi_str_mv | 10.1016/j.bmc.2010.02.044 |
| format | Article |
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Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed α-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38–1.86μM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G1 phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2010.02.044</identifier><identifier>PMID: 20231098</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Annexin A5 - metabolism ; Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antitumor agents ; Biological and medical sciences ; Blotting, Western ; Catalpol ; Cell cycle ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Enzyme Inhibitors - metabolism ; General aspects ; Glucosides - chemical synthesis ; Glucosides - chemistry ; Glucosides - pharmacology ; Humans ; Iridoid Glucosides ; Iridoids - chemical synthesis ; Iridoids - chemistry ; Iridoids - pharmacology ; Medical sciences ; Models, Molecular ; Molecular Conformation ; Molecular simplification ; Pharmacology. Drug treatments ; Structure elucidation ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry, 2010-04, Vol.18 (7), p.2515-2523</ispartof><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-30c945603fd3818602e42807502b75301a431fcdb84cba80f4d0bc4424a163c33</citedby><cites>FETCH-LOGICAL-c382t-30c945603fd3818602e42807502b75301a431fcdb84cba80f4d0bc4424a163c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0968089610001756$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22830995$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20231098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>García, Celina</creatorcontrib><creatorcontrib>León, Leticia G.</creatorcontrib><creatorcontrib>Pungitore, Carlos R.</creatorcontrib><creatorcontrib>Ríos-Luci, Carla</creatorcontrib><creatorcontrib>Daranas, Antonio H.</creatorcontrib><creatorcontrib>Montero, Juan C.</creatorcontrib><creatorcontrib>Pandiella, Atanasio</creatorcontrib><creatorcontrib>Tonn, Carlos E.</creatorcontrib><creatorcontrib>Martín, Víctor S.</creatorcontrib><creatorcontrib>Padrón, José M.</creatorcontrib><title>Enhancement of antiproliferative activity by molecular simplification of catalpol</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Molecular simplification of any given natural or synthetic template helps medicinal chemists designing shorten synthetic routes while keeping or enhancing the biological activity. This strategy is exemplified with simplified analogs of naturally occurring catalpol.
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed α-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38–1.86μM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G1 phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.</description><subject>Annexin A5 - metabolism</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor agents</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Catalpol</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>General aspects</subject><subject>Glucosides - chemical synthesis</subject><subject>Glucosides - chemistry</subject><subject>Glucosides - pharmacology</subject><subject>Humans</subject><subject>Iridoid Glucosides</subject><subject>Iridoids - chemical synthesis</subject><subject>Iridoids - chemistry</subject><subject>Iridoids - pharmacology</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Molecular Conformation</subject><subject>Molecular simplification</subject><subject>Pharmacology. Drug treatments</subject><subject>Structure elucidation</subject><subject>Structure-Activity Relationship</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtKxDAUhoMozjj6AG6kG3HVenJpm-BKhvECAyLoOqRpihnSi0krzNubYUbduTrnwPf_HD6ELjFkGHBxu8mqVmcE4g0kA8aO0ByzgqWUCnyM5iAKngIXxQydhbABAMIEPkUzAoRiEHyOXlfdh-q0aU03Jn2TqG60g--dbYxXo_0yidJx2HGbVNuk7Z3Rk1M-CbYdImR1hPpul4ybckPvztFJo1wwF4e5QO8Pq7flU7p-eXxe3q9TTTkZUwpasLwA2tSUY14AMYxwKHMgVZlTwIpR3Oi64kxXikPDaqg0Y4QpXFBN6QLd7Hvju5-TCaNsbdDGOdWZfgqypDQvy1LgSOI9qX0fgjeNHLxtld9KDHInUm5kFCl3IiUQGUXGzNWhfapaU_8mfsxF4PoAqKCVa3y0aMMfRzgFIfLI3e05E118WeNl0NZE47X1Ro-y7u0_b3wDobKQGg</recordid><startdate>20100401</startdate><enddate>20100401</enddate><creator>García, Celina</creator><creator>León, Leticia G.</creator><creator>Pungitore, Carlos R.</creator><creator>Ríos-Luci, Carla</creator><creator>Daranas, Antonio H.</creator><creator>Montero, Juan C.</creator><creator>Pandiella, Atanasio</creator><creator>Tonn, Carlos E.</creator><creator>Martín, Víctor S.</creator><creator>Padrón, José M.</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>20100401</creationdate><title>Enhancement of antiproliferative activity by molecular simplification of catalpol</title><author>García, Celina ; León, Leticia G. ; Pungitore, Carlos R. ; Ríos-Luci, Carla ; Daranas, Antonio H. ; Montero, Juan C. ; Pandiella, Atanasio ; Tonn, Carlos E. ; Martín, Víctor S. ; Padrón, José M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-30c945603fd3818602e42807502b75301a431fcdb84cba80f4d0bc4424a163c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Annexin A5 - metabolism</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor agents</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Catalpol</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>General aspects</topic><topic>Glucosides - chemical synthesis</topic><topic>Glucosides - chemistry</topic><topic>Glucosides - pharmacology</topic><topic>Humans</topic><topic>Iridoid Glucosides</topic><topic>Iridoids - chemical synthesis</topic><topic>Iridoids - chemistry</topic><topic>Iridoids - pharmacology</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Molecular Conformation</topic><topic>Molecular simplification</topic><topic>Pharmacology. Drug treatments</topic><topic>Structure elucidation</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>García, Celina</creatorcontrib><creatorcontrib>León, Leticia G.</creatorcontrib><creatorcontrib>Pungitore, Carlos R.</creatorcontrib><creatorcontrib>Ríos-Luci, Carla</creatorcontrib><creatorcontrib>Daranas, Antonio H.</creatorcontrib><creatorcontrib>Montero, Juan C.</creatorcontrib><creatorcontrib>Pandiella, Atanasio</creatorcontrib><creatorcontrib>Tonn, Carlos E.</creatorcontrib><creatorcontrib>Martín, Víctor S.</creatorcontrib><creatorcontrib>Padrón, José M.</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</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>García, Celina</au><au>León, Leticia G.</au><au>Pungitore, Carlos R.</au><au>Ríos-Luci, Carla</au><au>Daranas, Antonio H.</au><au>Montero, Juan C.</au><au>Pandiella, Atanasio</au><au>Tonn, Carlos E.</au><au>Martín, Víctor S.</au><au>Padrón, José M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enhancement of antiproliferative activity by molecular simplification of catalpol</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2010-04-01</date><risdate>2010</risdate><volume>18</volume><issue>7</issue><spage>2515</spage><epage>2523</epage><pages>2515-2523</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>Molecular simplification of any given natural or synthetic template helps medicinal chemists designing shorten synthetic routes while keeping or enhancing the biological activity. This strategy is exemplified with simplified analogs of naturally occurring catalpol.
Two iridoid scaffolds were synthesized enantioselectively using as key step an l-proline-catalyzed α-formyl oxidation. The in vitro antiproliferative activities were evaluated against a representative panel of human solid tumor cell lines. Both iridoids induced considerably growth inhibition in the range 0.38–1.86μM. Cell cycle studies for these compounds showed the induction of cell cycle arrest at the G1 phase. This result was consistent with a decrease in the expression of cyclin D1. Damaged cells underwent apoptosis as indicated by specific Annexin V staining.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>20231098</pmid><doi>10.1016/j.bmc.2010.02.044</doi><tpages>9</tpages></addata></record> |
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| subjects | Annexin A5 - metabolism Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antitumor agents Biological and medical sciences Blotting, Western Catalpol Cell cycle Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Enzyme Inhibitors - metabolism General aspects Glucosides - chemical synthesis Glucosides - chemistry Glucosides - pharmacology Humans Iridoid Glucosides Iridoids - chemical synthesis Iridoids - chemistry Iridoids - pharmacology Medical sciences Models, Molecular Molecular Conformation Molecular simplification Pharmacology. Drug treatments Structure elucidation Structure-Activity Relationship |
| title | Enhancement of antiproliferative activity by molecular simplification of catalpol |
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