ginkgolic-acid and anacardic-acid

Protein modification by small ubiquitin-related modifier proteins (SUMOs) controls diverse cellular functions. Dysregulation of SUMOylation or deSUMOylation processes has been implicated in the development of cancer and neurodegenerative diseases. However, no small-molecule inhibiting protein SUMOylation has been reported so far. Here, we report inhibition of SUMOylation by ginkgolic acid and its analog, anacardic acid. Ginkgolic acid and anacardic acid inhibit protein SUMOylation both in vitro and in vivo without affecting in vivo ubiquitination. Binding assays with a fluorescently labeled probe showed that ginkgolic acid directly binds E1 and inhibits the formation of the E1-SUMO intermediate. These studies will provide not only a useful tool for investigating the roles of SUMO conjugations in a variety of pathways in cells, but also a basis for the development of drugs targeted against diseases involving aberrant SUMOylation.

Topics: Anacardic Acids; Ginkgo biloba; Plant Extracts; Plant Leaves; Protein Binding; Salicylates; Small Molecule Libraries; Small Ubiquitin-Related Modifier Proteins; Structure-Activity Relationship; Ubiquitination

On the basis of antibacterial anacardic acids, 6-pentadecenylsalicylic acids, isolated from the cashew apple, Anacardium occidentale L. (Anacardiaceae), a series of 6-alk(en)ylsalicylic acids were synthesized and tested for their antibacterial activity against Streptococcus mutans ATCC 25175. Among them, 6-(4',8'-dimethylnonyl)salicylic acid was found to exhibit the most potent antibacterial activity against this cariogenic bacterium with the minimum inhibition concentration (MIC) of 0.78 microg/ml.

Topics: Anacardic Acids; Anti-Bacterial Agents; Dental Caries; Drug Design; Drug Evaluation, Preclinical

Five compounds, which inhibited the amidolytic activity of soluble tissue factor/activated factor VII complex (sTF/VIIa), were isolated from two traditional Chinese medicinal plants commonly used in the treatment of cardiovascular and cerebrovascular diseases. The active compounds were found to be linolenic, linoleic, and oleic acids from roots of Salvia miltiorrhiza; and two anacardic acids, 6-(8'Z-pentadecenyl)- and 6-(10'Z-heptadecenyl)-salicylic acids, from leaves of Ginkgo biloba. The IC50 values were in the range 30-80 micromol/L. Palmitic acid, isolated from roots of Salvia miltiorrhiza, and 2-[(3',7',11',15'-tetramethyl)-2'E,6'E,10'E, 14'E-hexadecatetraenyl]-1,4-hydroquinone, isolated from the marine sponge Adocia viola, did not inhibit sTF/VIIa. Further expansion of the structure-activity relationship to include anacardic acids, 6-(8'Z,11'Z-heptadecadienyl)- and 6-(8'Z, 11'Z, 14'Z-heptadecatrienyl)-salicylic acids from leaves of Anacardium spondias, and other fatty acids demonstrated that at least one cis double bond was essential for inhibitory activity, and that fatty acids containing two or three cis double bonds were optimal. Evidence from preincubation studies implied that these fatty acids may exert their effect by binding to VIIa and consequently preventing binding of sTF to VIIa.

Topics: Anacardic Acids; Enzyme Inhibitors; Factor VIIa; Fatty Acids, Unsaturated; Humans; Plant Extracts; Plant Roots; Plants, Medicinal; Recombinant Proteins; Salicylates; Trypsin Inhibitors

Anacardic acids, 2-methylcardols, and cardols isolated from various parts of the cashew [Anacardium occidentale] (Anacardiaceae) fruit have been found to exhibit tyrosinase inhibitory activity. Kinetic studies with the two principal active compounds, 6-[8(Z),11(Z),14-pentadecatrienyl]salicylic acid and 5-[8(Z),11(Z),14-pentadecatrienyl]resorcinol, have indicated that both of these phenolic compounds exhibit characteristic competitive inhibition of the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by mushroom tyrosinase.

Topics: Anacardic Acids; Basidiomycota; Kinetics; Levodopa; Monophenol Monooxygenase; Nuts; Oxidation-Reduction; Resorcinols; Salicylates; Structure-Activity Relationship