Three new and bioactive icosanoids from the temperate red marine algaFarlowia mollis

Abstract

Three new dihydroxyicosanoids, 12(R),13(R)-dihydroxyicosa-5(Z),8(Z),10(E),14(Z)-tetraenoic acid, 12(R),13(R)-dihydroxyicosa-5(Z),8(Z),10(E),14(Z),17(Z)-pentaeno ic acid and 10(R*),11(R*)-dihydroxyoctadeca-6(Z),8(E),12(Z)-trienoic acid, have been isolated from a previously unstudied temperate red marine alga, Farlowia mollis (Cryptonemiales, Rhodophyta). The structures of these new metabolites have been deduced from detailed nuclear magnetic resonance and mass spectrometry analyses on stabilized diacetate-methyl esters and stereochemistry deduced by 1H NMR couplings and CD analysis of a dibenzoate derivative. Collectively, these new natural products modulate fMLP-induced superoxide anion generation in human neutrophils, inhibit the conversion of arachidonic acid to lipoxygenase products by human neutrophils, and inhibit the functioning of the dog kidney Na+/K+ ATPase.

Biologically active oxylipins from seaweeds

“…As originally reported (Solem et al, 1989), a mixture of 2 and 3 was weakly inhibitory to human 5-lipoxygenase obtained from polymorphonuclear leukocytes and showed some inhibition of the dog kidney derived Na + /K + ATPase. More recently, we have discovered that the methyl ester of pure metabolite 3 is effective at causing a pronounced reduction in serum progesterone in female sheep in their tenth day of estrous (injection into ovarian artery), similar to the action of prostaglandin PGF 2 ,, This is accompanied by a greater number of treated animals entering estrus 3 days after injection than control treated sheep (methyl eicosapentaenoate).…”

Eicosanoids from the Rhodophyta: new metabolism in the algae

“…Two temperate red algae from the Oregon coast, products during our survey of Pacific Northwest algae for new biomedicinal agents (Gerwick et al, work in progress) . Subsequently, we have isolated a series of novel eicosanoid metabolites containing a vicinal diol functionality from both of these algae, compound 9 being an example (Solem et al, 1989). The location of these oxidized sites again suggests the involvement of a 12-LO reaction in their biosynthesis .…”

Algal Secondary Metabolites and Their Pharmaceutical Potential

“…Phytochemical investigations of red algae have resulted in the identification of a predominance of halogenated metabolites, which are mainly of terpenoid, acetogenic or aromatic origin (72). Marine red algae have also been recognized as a source of structurally varied icosanoic acid derivatives (45)(46)(47)(48)(49)(50). Biological activities discovered for red algal metabolites include antimicrobial, cytotoxic, anti-inflammatory and antiviral effects, as well as inhibition of canine Na + /K + ATPase, human lymphocyte 5-lipoxygenase and human neutrophil degranulation (48).…”

“…A mixture of 12/?,13S-dihydroxyicosatetraenoic acid and 12i?,13S-dihydroxypentaenoic acid (42), isolated from Farlowia mollis (Cryptonemiales) was shown to inhibit human lymphocyte 5-lipoxygenase, dog kidney Na + /K+ ATPase, and to modulate fMLPinduced superoxide anion generation in human neutrophils (48). 125-HEPE is a strong inhibitor of platelet aggregation and a mediator of inflammation (47).…”

“…Recent studies with synthetic icosapentaenoic acids showed that these compounds selectively modulate the human platelet thromboxane Ayprostaglandin H 2 receptor (84). Some of these unsaturated arachidonic acid metabolites also show antimicrobial activity (46,48). Icosanoids have also been obtained from marine sponges (85,86) and from starfish (87).…”