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A reversed-phase high-performance liquid chromatography/diode-array detector procedure is proposed for the determination of six phenolic compounds (caffeic acid, luteolin 7-O-glucoside, rosmarinic acid, apigenin, hispidulin, and cirsimaritin) in sage. The chromatographic separation was achieved using a reversed-phase Spherisorb ODS2 (5-microm particle size, 25.0 x 0.46 cm) column. Of the several extractive solvents assayed only ethyl ether, ethyl acetate, and acetone were able to extract all the compounds mentioned. Best resolution was obtained using a gradient of water/phosphoric acid (999:1) and acetonitrile. Ten samples cultivated in two experimental fields (1997-1999) were analyzed and the individual compounds quantified. Four commercially available samples were also analyzed and the results are discussed.

The reaction of salicylic aldehydes with malononitrile was reinvestigated, and the reaction pathway was followed by 1H NMR spectroscopy. A delicate control of the experimental conditions allowed the synthesis of 2-imino-2H-chromene-3-carbonitriles 1, (2-amino-3-cyano-4H-chromen-4-yl)malononitriles 2, 4-amino-5-imino-2,7-dimethoxy-5H-chromeno[3,4-c]pyridine-1-carbonitrile 12, and (4,5-diamino-1-cyano-1,10b-dihydro-2H-chromeno[3,4-c]pyridin-2-ylidene)malononitrile 13. Two novel 2-iminochromene dimers, with structures 8 and 9, were isolated and fully characterized. The activity of compound 8a on Aspergillus spp. growth and on ochratoxin A production was evaluated. The results of the bioassays indicate that compound 8a, applied at concentrations of 2 mM, totally inhibited the growth of the fungi tested. Ochratoxin A production by Aspergillus alliaceus was reduced by about 93% with a 200 microM solution of this compound. A moderate inhibitory effect was observed for the analogous structure 8b, and no inhibition was registered for compounds 2 and 1, used as synthetic precursors of the dimeric species 8.

A reversed-phase HPLC procedure is proposed for the determination of seven flavonoids (luteolin, nepetin, hispidulin, jaceosidin, cirsimaritin, cirsilineol, and eupatorin) in vervain samples. A simple extractive technique was developed, involving only extraction with ethyl ether, which allowed the elimination of phenolic acids, yielding a sufficiently purified flavonoid fraction. All of the analyzed vervain samples showed a common flavonoid pattern, in which hispidulin and jaceosidin were the major compounds and nepetin was the minor compound.

In this study we used new nitrogen compounds obtained by organic synthesis whose structure predicted an antioxidant potential and then an eventual development as molecules of pharmacological interest in diseases involving oxidative stress. The compounds, identified as FMA4, FMA5, FMA7 and FMA8 differ in the presence of hydroxyl groups located in the C-3 and/or C-4 position of a phenolic unit, which is possibly responsible for their free radicals' buffering capacity. Data from the DPPH discoloration method confirm the high antiradical efficiency of the compounds. The results obtained with cellular models (L929 and PC12) show that they are not toxic and really protect from membrane lipid peroxidation induced by the ascorbate-iron oxidant pair. The level of protection correlates with the drug's lipophilic profile and is sometimes superior to trolox and equivalent to that observed for alpha-tocopherol. The compounds FMA4 and FMA7 present also a high protection from cell death evaluated in the presence of a staurosporine apoptotic stimulus. That protection results in a significant reduction of caspase-3 activity induced by staurosporine which by its turn seems to result from a protection observed in the membrane receptor pathway (caspase-8) together with a protection observed in the mitochondrial pathway (caspase-9). Taken together the results obtained with the new compounds, with linear chains, open up perspectives for their use as therapeutical agents, namely as antioxidants and protectors of apoptotic pathways. On the other hand the slight pro-oxidant profile obtained with the cyclic structures suggests a different therapeutic potential that is under current investigation.

A series of 37 benzolactam derivatives were synthesized, and their respective affinities for the dopamine D(2) and D(3) receptors evaluated. The relationships between structures and binding affinities were investigated using both ligand-based (3D-QSAR) and receptor-based methods. The results revealed the importance of diverse structural features in explaining the differences in the observed affinities, such as the location of the benzolactam carbonyl oxygen, or the overall length of the compounds. The optimal values for such ligand properties are slightly different for the D(2) and D(3) receptors, even though the binding sites present a very high degree of homology. We explain these differences by the presence of a hydrogen bond network in the D(2) receptor which is absent in the D(3) receptor and limits the dimensions of the binding pocket, causing residues in helix 7 to become less accessible. The implications of these results for the design of more potent and selective benzolactam derivatives are presented and discussed.

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