ABSTRACT
N-trans- and N-cis-Feruloyltyramines were isolated as the inhibitors of in vitro prostaglandin (PG) synthesis from an Indonesian medicinal plant, Ipomoea aquatica (Convolvulaceae). In order to clarify structure activity relationships, cinnamoyl-beta-phenethylamines with possible combinations of naturally occurring cinnamic acids and beta-phenethylamines were synthesized and tested for their inhibitory activities against PG synthetase and arachidonate 5-lipoxygenase. The compounds containing catechol groups such as N-caffeoyl-beta-phenethylamine (CaP) showed higher inhibitory effects on PG synthetase. The catechol group was found to be essential for the inhibition of arachidonate 5-lipoxygenase. The investigation of concentration dependent effects on PG biosynthesis revealed that CaP enhanced PG biosynthesis at a lower concentration range, whereas it inhibited the reaction at a higher concentration. The effects of CaP on each reaction step were investigated with purified PG endoperoxide synthase and microsomal PG synthetase. CaP inhibited the cyclooxygenase reaction, while it enhanced the hydroperoxidase reaction. N-Acyldopamines which contain catechol and lipophylic group were synthesized from dopamine and fatty acids to test their inhibitory effects on arachidonate 5-lipoxygenase. N-Linoleoyldopamine was the most active compound and its IC50 value was 2.3 nM in our assay system, in which an IC50 value of AA 861, a specific inhibitor of 5-lipoxygenase, was 8 nM.
Subject(s)
Cinnamates/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Dopamine/analogs & derivatives , Lipoxygenase Inhibitors/pharmacology , Phenethylamines/pharmacology , Plants, Medicinal/chemistry , Cinnamates/chemistry , Cyclooxygenase Inhibitors/chemistry , Dopamine/chemistry , Dopamine/pharmacology , Lipoxygenase Inhibitors/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Phenethylamines/chemistry , Structure-Activity RelationshipABSTRACT
1. An unknown compound which is very similar to taurine was detected in the extract of sardine Sardinops melanosticta. 2. It was identified as D-cysteinolic acid: 2-amino-3-hydroxy-1-propanesulfonic acid from instrumental analysis. 3. This may be the first report in which the occurrence of D-cysteinolic acid in fish has been demonstrated. 4. Of 14 species of fish and shellfish examined, the presence of this compound was confirmed in 7 species.
