Impact of stereochemistry on the biological activity of novel oleandomycin derivatives
| Autor: | Mark B Vine, Martina Bosnar, Goran Kragol, Ivanka Pašalić, Ognjen Čulić, Gorjana Lazarevski, Jurica Bauer, Ilija Čorić, Gordana Turkalj |
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| Rok vydání: | 2012 |
| Předmět: |
Lipopolysaccharides
Male Neutrophils Stereochemistry Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science Stereoisomerism Microbial Sensitivity Tests Gram-Positive Bacteria Macrolide Configuration determination Biological activity Inflammation Biochemistry Cell Line Mice In vivo Gram-Negative Bacteria Drug Discovery medicine Animals Molecular Biology Mice Inbred BALB C Oleandomycin Interleukin-6 Chemistry Organic Chemistry In vitro Anti-Bacterial Agents Molecular Medicine Stereoselectivity Antibacterial activity Two-dimensional nuclear magnetic resonance spectroscopy Spleen medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 20:2274-2281 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2012.02.013 |
| Popis: | A set of 8-methylene-, 8-methyl-, and 8-methyl- 9-dihydro-oleandomycin derivatives having different combinations of stereochemistries at positions C-8 and/or C-9 have been prepared in a chemoselective and stereoselective manner and tested in vitro for antibacterial activity and inhibition of IL-6 production. Configurations of the stereocenters at C-8 and C-9 were determined using 2D NMR techniques. We have shown that change of stereochemistry at these positions can exert a major influence on antibacterial activity as well as IL-6 inhibition, providing novel macrolide derivatives with diminished antibacterial and potent anti-inflammatory activity. In addition, the anti-inflammatory activity observed in vitro was confirmed in an in vivo model of lipopolysaccharide-induced inflammation. |
| Databáze: | OpenAIRE |
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