Leukotriene biosynthesis inhibition by aryl and aroyl substituted naphthoquinones
- 22 Downloads
Naphthoquinones are known to inhibit 5-lipoxygenase. In particular, CGS 8515 (methyl 2-[(3,4-dihydro-3,4-dioxo-1-naphthalenyl)amino]benzoate) has been studied in detail. However this potent and selective 5-lipoxygenase inhibitor has a short duration of action and poor bioavailability. To improve the duration of action we have prepared a series of carbon substituted naphthoquinones. Several members of this series have demonstrated potentin vitro inhibition of 5-LO (IC50's<10−6M) and at doses of 1 mg/kg iv completely inhibited LTB4 production measured inex vivo A23187-stimulated blood from dogs. The duration of action measured by theex vivo assay was improved up to threefold over CGS 8515.
KeywordsMethyl Short Duration LTB4 Naphthoquinones Biosynthesis Inhibition
Unable to display preview. Download preview PDF.
- E. F. Kimble, D. H. White, W. H. Lee, E. C. Ku and T. D. Oglesby,Biochemical evaluation of 5-lipoxygenase in the beagle dog in vitro and ex vivo. 4th International Conference, Inflammation Research Association: Poster #87 (1988).Google Scholar