Arachidonic acid oedema

A series of 4-arylpyrimidines that arc amine substituted at pyrimidine C-2 was prepared. FK360 was most effective from this group on both arachidonate-induced cerebral oedema in rats and as an in vitro inhibitor of lipid peroxidation. The authors link effects of FK360 to the arachidonic acid cascade (Kuno et al., 1992). This is an unusual structure. 

AAE arachidonic acid-induced ear oedema CPE carrageenan paw oedema... 

Manoalide (164), a marine natural product which inhibits the release of arachidonic acid from phospholipids by phospholipase A2 [397,398], showed topical anti-inflammatory activity in mouse ear models [399]. Activity in ISN and cRBL (< 1 M) have also been reported [400]. A series of analogues consisting of the furanone ring of manoalide bearing simple unsaturated 16-20 carbon chains showed similar activity in rabbit neutrophils and isolated guinea-pig neutrophil 5-LO [401] interestingly, however, topical anti-inflammatory activity was seen in phorbol ester ear oedema but not in AAE [399]. The importance of 5-LO inhibition to the anti-inflammatory activity of manoalide is unknown effects on phospholipase C and calcium channels have also been shown [402, 403]. 

In 1998, Sciuto and Stotts showed that post-treatment of guinea pigs with 5,8,11,14-eicosatetraynoic acid (ETYA) reduced pulmonary artery pressure after exposure to phosgene. ETYA is a competitive analogue of arachidonic acid and blocks the formation of arachidonic acid-derived mediators. Not all of the results of this study proved easy to interpret ETYA decreased lipid peroxidation (as measured by TBARS formation) and decreased oedema formation but increased leukotiene release. The authors account should be examined for details but the importance of possible species-specific effects is noted here. 

Three new oleanane saponins from Zahna africana (63-65) were active against a TPA-induced ear oedema, exhibiting ID50 of 14, 20 and 79 i.g/ear, respectively [90]. Tubeimoside III, natural analog of tubeimoside I (5) also had an antiinflammatory effect on mouse oedema induced by arachidonic acid and TPA [39],... 

Compounds 34 and 35 were found to be inhibitors of 5-lipoxygenase and cyclooxygenase-1 and -2. The closely related derivative 36, was, however, found to be a selective inhibitor of 5-Iipoxygenase. Topical application of 36 significantly suppressed both arachidonic acid- and 12-0-tetradecanoyl phorbol 13-acetate-induced ear oedemas in mice [17]. 

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