| Drug-phospholipid conjugates as potential prodrugs: synthesis, characterization, and degradation by pancreatic phospholipase A(2). | |
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MedLine Citation:
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PMID: 11090844 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of the present study was the synthesis of phospholipids containing a drug molecule instead of a fatty acid. Valproic acid and ibuprofen served as model compounds. The target molecules were synthesized either starting from sn-glycero-3-phosphocholine (1) or using (S)-2-O-benzyl-1-O-tritylglycerol (11) and (R)-2-O-benzyl-1-O-tert-butyldiphenylsilylglycerol (12), respectively, as key intermediates. With respect to the surface properties and the aggregation behavior, the drug-phospholipid conjugates resembled natural phosopholipids. Upon incubation with porcine pancreatic phospholipase A(2), only compounds with a fatty acid in the sn-2 position of the glycerol backbone were degraded. Derivatives with either ibuprofen in the sn-2 position or displaying the unnatural S-configuration were resistant to enzymatic in vitro hydrolysis. |
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Authors:
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M Kurz; G K Scriba |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemistry and physics of lipids Volume: 107 ISSN: 0009-3084 ISO Abbreviation: Chem. Phys. Lipids Publication Date: 2000 Oct |
Date Detail:
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Created Date: 2000-12-04 Completed Date: 2000-12-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0067206 Medline TA: Chem Phys Lipids Country: IRELAND |
Other Details:
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Languages: eng Pagination: 143-57 Citation Subset: IM |
Affiliation:
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University of Münster, Department of Pharmaceutical Chemistry, D-48149, Münster, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Hydrolysis Ibuprofen / chemistry* Magnetic Resonance Spectroscopy Mass Spectrometry Pancreas / enzymology* Phospholipases A / metabolism* Phosphorylcholine / chemistry* Prodrugs / chemical synthesis*, chemistry, metabolism Valproic Acid / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Prodrugs; 107-73-3/Phosphorylcholine; 15687-27-1/Ibuprofen; 99-66-1/Valproic Acid; EC 3.1.1.-/Phospholipases A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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