Manoalide isolation

Cyclohexane sesterterpenes are formally derived from 3,7,11,15,19-pentamethyl-icosane by connection of the C-14-C-19 bond. A few representatives are found in various marine sponges. The lactone (-)-manoalide isolated from the sponge Luf-... 

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]. 

Problem 29.1 2 Manoalide, a sesterterpene isolated from the Pacific marine sponge Luffariella veriabills by Scheuer and co-workers at the University of Hawai i at Manoa, has anti-inflammatory, analgesic, and antifungal properties. Find the isoprene units in manoalide. 

From the Western Pacific sponge L. variabilis was isolated dehydro-manoalide (57) that showed a marked decrease in inhibition of bee venom PLA2 (IC50 0.28 pM) [76, 87],... 

Kobayashi and co-workers [70] reported, from the Okinawan sponge Luffariella sp., the isolation of several sesterterpenoids related to manoalide, named luffariolides A-J (59-67). All luffariolides showed cytotoxic activity against L1210 cells (IC50 1.1-4.5 pg/ml) and only luffariolides F (64) and G (65) exhibited weak activity also against KB... 

In order to provide sufficient manoalide for continued pharmacological evaluation, F aulkner and coworkers made an extensive c ollection of L. variabilis, from different locations in Palau. From a small number of specimens of L. variabilis were isolated two new metabolites, luffariellin A (77) and Luffariella B (78) in place of manoalide and seco-manoalide [97], Despite the different carbon skeleton, the functional groups in luffariellins A and B are identical with those in manoalide and seco-manoalide, respectively, and they showed almost identical antiinflammatory properties. Both luffariellins were potent antagonists of topical induced inflammation in the mouse ear, and inhibitors of bee venom PLA2, with an IC50 value of 5.6 x 10 8 M and 6.2 x 10 8 M, for luffariellins A and B, respectively [97]. 

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