Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine.

New amides of different fatty acids from the C18, C20, and C22 series with dopamine were synthesized. Pharmacological characterization in binding assays with rat brain membrane preparations and in the 'tetrad' of cannabinoid behavioral tests showed that, for these compounds, cannabinoid-like activity was dependent on the fatty acid moiety. Our data demonstrate that polyenoic fatty acid amides with dopamine comprise a new family of synthetic cannabimimetics.

[Factors, determining the activity of a new antimicrobial substance from fish oils from various species]. / Faktory, opredeliaiushchie aktivnost' novogo antimikrobnogo preparata iz rybnykh zhirov razlichnoi prirody.

The induction of antimicrobial activity of a new preparation, an aqueous fraction of water-oil emulsion oxidized by air oxygen, was studied. The effect of various factors (the degree of unsaturation of the initial oil and the content of oil oxidation products in obtained preparation) on the antimicrobial activity was determined. The antimicrobial activity of the preparation was induced by oil oxidation. The preparation produced from sardine Sardinops melanostica oil (33.95% of polyunsaturated fatty acids) displayed the highest antimicrobial activity. The antimicrobial activity was shown in water-soluble oil oxidation products.

Hydrolysis of anandamide and eicosapentaenoic acid ethanolamide in mouse splenocytes.

The hydrolysis of anandamide has been studied in mouse splenocytes using tritiated anandamide analogs labeled in the acyl- or ethanolamide parts of the molecule. [3H]Anandamide undergoes rapid (t(1/2) = 2.5 min) uptake and hydrolysis, yielding ethanolamine and arachidonic acid. The anandamide hydrolysis in splenocytes is sensitive to inhibition by phenylmethylsulfonyl fluoride, and it is assumed that the observed activity is due to fatty acid amide hydrolase, which inactivates anandamide in central and peripheral tissues. Eicosapentaenoic acid ethanolamide and the 15-hydroxy-derivative of anandamide are shown to be amidohydrolase substrates as well. The fatty acids derived from hydrolytic cleavage of acylethanolamines undergo rapid oxidation by splenocyte lipoxygenase, yielding the corresponding 12-hydroxy-derivatives. Oxygenated ethanolamide derivatives were not found. The data suggest that polyenoic fatty acid ethanolamides are metabolic precursors of eicosanoids in splenocytes and that amide bond hydrolysis is the key point in switching of biological activity spectra between endocannabinoids and oxylipins.

[(2E)-4-hydroxy-2-nonenal--an active component of a new natural antimicrobial substance]. / (2E)-4-gidroksi-2-nonenal'--aktivnyi komponent novogo prirodnogo antimikrobnogo preparata.

A mixture of water-soluble oxidation products of Sardinops melanosticta sardine oil was found to contain (2E)-4-hydroxy-2-nonenal. This was isolated by column chromatography on silica gel and reversed-phase HPLC. Its structure was elucidated by physicochemical methods. The activity of (2E)-4-hydroxy-2-nonenal against test cultures of Escherichia coli, Staphylococcus aureus, and Bacillus subtilis was about 20% of the total antimicrobial activity of the preparation.

[Artificially functionalized polyenoic fatty acids--a new lipid bioregulators]. / Iskusstvenno funktsionalizirovannye polienovye zhirnye kisloty-- novye lipidnye bioreguliatory.

Dopamine, histamine, serotonin, and serotonin analogs were acylated with arachidonic and eicosapentaenoic acids, and the reaction products were named as artificially functionalized fatty acids (AFFA). The amides of arachidonic acid with serotonin, dopamine, and histamine were found to inhibit human platelet aggregation induced by ADP, arachidonic acid and adrenaline. Amides of arachidonic and eicosapentaeonic acids with serotonin and dopamine protect sea urchin early embryos against cytotoxic action of serotonin and histamine antagonists. These effects are not connected with the possible hydrolytic cleavage of AFFA to their constituent polyenoic fatty acids and amines. Arachidonic acid dopaminamide was shown to be a substrate of soybean 15-lipoxygenase, whereas the arachidonic acid amides with serotonin and its derivatives were resistant to this enzyme. Moreover, arachidonic acid serotoninamide turned out to be an irreversible lipoxygenase inhibitor. Considerable amount of hydroxyl radicals (fluorescent assay) were found for the first time to accompany lipoxygenase oxidation of linoleic acid; arachidonic acid serotoninamide blocked this process completely. Therefore, it was concluded that AFFA possess specific biological activity and can be considered as a novel group of lipid bioregulators.

[Synthesis of monoepoxides of arachidonic, eicosapentaenoic, and docosahexaenoic acids]. / Sintez monoépoksidov arakhidonovoi, éikozapentaenovoi i dokozageksaenovoi kislot.

A practical synthesis of cis-monoepoxides from free arachidonic 20:4 (n-6), eicosapentaenoic 20:5 (n-3) and docosahexaenoic 22:6 (n-3) acids, their cytochrome P-450 epoxygenase metabolites, is described. The free polyunsaturated fatty acids (PUFA) were oxidized each by 1.25 eq. m-chloroperbenzoic acid in ethanol to give a mixture of PUFAs' mono-epoxy derivatives (45%) which was separated by HPLC and the individual isomers were characterised by mass spectrometry. All regioisomers of the free PUFAs' cis-monoepoxides were thus obtained.