Dimethyleicosatrienoic acids: Inhibitors of the 5-lipoxygenase enzyme

✍ Scribed by Carl D. Perchonock; Joseph A. Finkelstein; Irene Uzinskas; John G. Gleason; Henry M. Sarau; Lenora B. Cieslinski

• Publisher: Elsevier Science
• Year: 1983
• Tongue: French
• Weight: 190 KB
• Volume: 24
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)81954-1

✦ Synopsis

Syntheses of 7,7-and 10,10-dimethyleicosa-5(Z1,8(Z),ll(Z1-trienoic acids (zand $1, which possess 5-lipoxygenase inhibitory activity, are described. Arachidonic acid (L) is now well established as a key substance in the biosynthesis of the leukotrienes, a family of compounds that have been implicated as mediators of asthma and inflammation.' It is oxidized by a 5-lipoxygenase enzyme to 5-hydroperoxyeicosatetraenoic acid (5-HPETE,zl, which, in turn, is converted to Leukotriene A4 (LTA4,z1 by a second enzyme, "LTA4 synthetase." LTA4 serves as a precursor to Leukotrienes B, C, D, and E, the last three being integral components of Slow Reacting Substance of Anaphylaxis (SRS-Al. Other polyunsaturated fatty acids also serve as suhstrates for the 5-lipoxygenase enzyme systen. In particular, Jakschik, et al.2 have demonstrated that 5,8,11-eicosatrienoic acid _-(2) is converted to a material with SRS activity, and the work of Hammarstrom3 strongly indicates that this material includes LTCS and LTDS, which have biological activity comparable to their tetraene counterparts.