Luffolide, a novel anti-inflammatory terpene from the spongeLuffariella sp.

Abstract

Luffolide (4) is a minor metabolite of the sponge Luffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products 5 and 6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A2.

Petrosaspongiolides M−R: New Potent and Selective Phospholipase A2 Inhibitors from the New Caledonian Marine Sponge Petrosaspongia nigra

“…The dichloromethane-soluble material was fractionated by Si gel flash chromatography (MPLC) eluting with CHCl 3 -MeOH mixtures with increasing amounts of MeOH, followed by reversedphase HPLC to yield petrosaspongiolides M-R (1)(2)(3)(4)(5) (yields: 58.3 mg, 2.7 mg, 47.8 mg, 2.5 mg, and 3.2 mg, respectively).…”

“…6,7 In our continuing search for bioactive substances from New Caledonian marine organisms, we have had occasion to analyze the extracts of the sponge Petrosaspongia nigra Bergquist 1995 sp.nov. (Dictyoceratida, Spongidae) collected off New Caledonia, from which we isolated five new sesterterpenes (1)(2)(3)(4)(5) named petrosaspongiolides M-R, along with a number of other cytotoxic sesterterpenes (petrosaspongiolides A-L), 8 all possessing a cheilantane skeleton. Herein we report their isolation, structure elucidation (see Tables 1 and 2 for NMR assignments), and the data from their in vitro tests on the inhibition of human sinovial, Naja naja venom, bee venom, and porcine pancreas PLA 2 (Table 3).…”

“…Five new bioactive sesterterpenes (1)(2)(3)(4)(5) have been isolated from the New Caledonian marine sponge Petrosaspongia nigra Bergquist and named petrosaspongiolides M-R. Their chemical structures were determined from 1D and 2D NMR studies and MS data. All compounds inhibited different preparations of phospholipase A 2 (PLA 2 ) by irreversibly blocking these enzymes (particularly human synovial and bee venom, see Table 3), with IC 50 values in the micromolar range.…”

PLA2 Mediated Arachidonate Free Radicals: PLA2 Inhibition and Neutralization of Free Radicals by Anti-Oxidants – A New Role as Anti-Inflammatory Molecule

“…Diterpenes includes gracilin A [76], 12-acetoxytetrahydro aplysulfurin-1 [77], aplyroseols-1,-5 and -6, norrisolide, dendrillolide A [78]. Some of the sesquiterpenes inhibiting PLA 2 are manoalide [79], scalaradial [80] and cacospongionolide B [81] and E [82], petrosaspongiolides M, N, P, Q and R, petrosaspongiolides A-L [83], 21-hydroxypetrosas-pongiolide K and P [84], palanolide [85] and luffolide [86]. The antiinflammatory activity of manoalide is due to inhibition of PLA 2 , through irreversible binding to several lysine residues.…”

Investigations of the Marine Flora and Fauna of the Islands of Palau

“…87 In contrast, the second specimen (from 1995) contained three 9,11-secosterols, luffasterols A 122-C, as well as manoalide 123 and secomanoalide 124. 88 Both 120 and 121 inhibited PLA 2 and were anti-inflammatory agents whilst luffasterol A 122 demonstrated activity in the NCI's 60 cell line panel.…”