Preparation of Novel Analogues of the Nonredox-Type Non-Competitive Leukotriene Biosynthesis Inhibitor AKBA
| Autor: | R. F. Hoernlein, Hermann P. T. Ammon, E.-R. Sailer, Lakshminarayanapuram R. Subramanian |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
chemistry.chemical_classification
biology Chemistry Stereochemistry Pharmaceutical Science Biological activity Primary alcohol biology.organism_classification chemistry.chemical_compound Enzyme Biochemistry Enzyme inhibitor Drug Discovery Arachidonate 5-lipoxygenase biology.protein Boswellia serrata Boswellic acid IC50 |
| Zdroj: | Archiv der Pharmazie. 329:54-56 |
| ISSN: | 1521-4184 0365-6233 |
| DOI: | 10.1002/ardp.19963290110 |
| Popis: | AKBA (acetyl-11-keto-β-boswellic acid, 1) and KBA (11-keto-β-BA, 2) from Boswellia serrata Roxb. and Boswellia carterii Birdw. are direct, nonredox-type inhibitors of 5-lipoxygenase, the key enzyme for leukotriene biosynthesis (IC50 = 1.5 and 3μM in intact neutrophils, respectively). In order to study the impact of the carboxyl function for enzyme inhibition, we synthesized novel analogues of boswellic acids. The C-4 alcohol derivative of KBA (4) still exerted 5-lipoxygenase inhibitory activity (IC50 = 4.5 μM), whereas (8), the C-4 alcohol analogue of β-boswellic acid (7), the methyl ester analogue of KBA (5), and acetyl-11-keto-amyrin (9) possessed no inhibitory potential in concentrations up to 50 μM. These findings reveal that a hydrophilic group at C4 in combination with an 11-keto-function is essential for 5-lipoxygenase inhibition by boswellic acids. |
| Databáze: | OpenAIRE |
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