ABSTRACT
The phytochemical investigation on the aereal parts of Lychnophora pinaster Mart., Asteraceae, was carried to isolation of triterpenes. 3-O-Acetyl-lupeol (1), 3-O-acetyl-pseudotaraxasterol (2), and 3-O-acetyl-α-amyrin (3) were isolated from hexanic extract and 4,4-dimethyl-cholesta-22,24-dien-5-ol (4), α-amyrin (5), and lupeol (6) were isolated from hexanic/dichlorometanic extract of the leaves. Compounds Δ7-bauerenyl acetate (7), friedelin (8), stigmasterol (9), and sitosterol (10) were isolated from the hexanic/dichlorometanic extract of the stems. The steroids 9 and 10 were also isolated from the hexanic/dichlorometanic extract of the flowers. Triterpenes 1, 3, 4, and 7 are described for the first time in the genus Lychnophora. The apolar fractions of the leaf and stem extracts and some isolated triterpenes showed low trypanocidal activity. Moreover, apolar fractions of the leaf and stem extracts and 5 showed antibacterial action against Staphylococcus aureus.
ABSTRACT
The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC50 of 48.5 æM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60 percent at 20 æg/ml (59 and 90 æM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 æg/ml (0.6-1.5 mM).
Subject(s)
Animals , Male , Mice , Furans/pharmacology , Enzyme Inhibitors/pharmacology , NADH, NADPH Oxidoreductases/antagonists & inhibitors , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Furans/chemistry , Enzyme Inhibitors/chemistry , Structure-Activity RelationshipABSTRACT
Fourteen compounds were evaluated for their activity against Trypanosoma cruzi blood stream forms at the concentration of 500 æg/ml. Six compounds were active and re-tested at lower concentrations