Enhancing Macrocyclic Diterpenes as Multidrug-Resistance Reversers: Structure–Activity Studies on Jolkinol D Derivatives
The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2–13) and hydrolysis to compound 14. The in vitro modulation of P-gp of compounds 1–14 was evaluated through a combination of transport and chemosensitivi...
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| Veröffentlicht in: | Journal of medicinal chemistry 2013-02, Vol.56 (3), p.748-760 |
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| container_title | Journal of medicinal chemistry |
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| creator | Reis, Mariana Ferreira, Ricardo J Santos, Maria M. M dos Santos, Daniel J. V. A Molnár, Joseph Ferreira, Maria-José U |
| description | The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2–13) and hydrolysis to compound 14. The in vitro modulation of P-gp of compounds 1–14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene. Apart from jolkinol D, all derivatives (2–14) showed potential as MDR reversal agents. In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure–activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents. |
| doi_str_mv | 10.1021/jm301441w |
| format | Article |
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In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure–activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm301441w</identifier><identifier>PMID: 23336337</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics ; Cell Line, Tumor ; Chromatography, Liquid ; Diterpenes - chemistry ; Diterpenes - pharmacology ; Drug Resistance, Multiple - drug effects ; Humans ; Macrocyclic Compounds - chemistry ; Macrocyclic Compounds - pharmacology ; Magnetic Resonance Spectroscopy ; Mice ; Spectrometry, Fluorescence ; Spectrometry, Mass, Electrospray Ionization ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 2013-02, Vol.56 (3), p.748-760</ispartof><rights>Copyright © 2013 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-1ea61b3eaf4a3285bef8ccc746bbd3bcde5de605ce8346bf5ddb9449dd8f83fb3</citedby><cites>FETCH-LOGICAL-a315t-1ea61b3eaf4a3285bef8ccc746bbd3bcde5de605ce8346bf5ddb9449dd8f83fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm301441w$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm301441w$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23336337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reis, Mariana</creatorcontrib><creatorcontrib>Ferreira, Ricardo J</creatorcontrib><creatorcontrib>Santos, Maria M. 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| ispartof | Journal of medicinal chemistry, 2013-02, Vol.56 (3), p.748-760 |
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| subjects | Animals ATP Binding Cassette Transporter, Sub-Family B ATP-Binding Cassette, Sub-Family B, Member 1 - genetics Cell Line, Tumor Chromatography, Liquid Diterpenes - chemistry Diterpenes - pharmacology Drug Resistance, Multiple - drug effects Humans Macrocyclic Compounds - chemistry Macrocyclic Compounds - pharmacology Magnetic Resonance Spectroscopy Mice Spectrometry, Fluorescence Spectrometry, Mass, Electrospray Ionization Structure-Activity Relationship |
| title | Enhancing Macrocyclic Diterpenes as Multidrug-Resistance Reversers: Structure–Activity Studies on Jolkinol D Derivatives |
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