2-Arylalkyl-substituted anthracenones as inhibitors of 12-lipoxygenase enzymes. 2. Structure-activity relationships of the linker chain
| Autor: | Helge Prinz, Klaus Müller, Reinhold Altmann |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Blood Platelets
Stereochemistry Swine In Vitro Techniques Chemical synthesis Lipoxygenase Mice Structure-Activity Relationship Drug Discovery Leukocytes Animals Lipoxygenase Inhibitors Skin Pharmacology chemistry.chemical_classification Anthracenes biology Organic Chemistry General Medicine In vitro Enzyme chemistry Biochemistry Enzyme inhibitor Arachidonate 5-lipoxygenase Lipophilicity biology.protein Cattle Linker |
| Zdroj: | European journal of medicinal chemistry. 37(1) |
| ISSN: | 0223-5234 |
| Popis: | A series of 2-arylalkyl-substituted anthracenones were tested as inhibitors of three types of 12-lipoxygenase isoforms in epidermal homogenate of mice, bovine platelets and porcine leukocytes. Their inhibitory activities were compared with those to inhibit the 5-lipoxygenase enzyme in bovine leukocytes. The compounds were synthesised by Marschalk, Wittig or Horner–Emmons reaction at the anthracenedione stage and then reduced to the anthracenones. Structure–activity relationship for the chain linking the anthracenone nucleus and the phenyl ring terminus was investigated. The 2-phenylethyl analogues were among the most potent inhibitors, and 3,4-dimethoxy-substituted 10f was identified as a selective inhibitor of the 12-LO enzymes over 5-LO. Selectivity for 12-LO isoforms was observed with an increase in the overall lipophilicity of the inhibitors. However, none of the linker chains of the 2-substituted anthracenones provided inhibitors that were able to discriminate between the 12-LO isoforms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect