Anti-Trypanosomal Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica.

The crude extract of Alnus japonica bark exhibited a strong effect on the growth of Trypanosoma brucei. Subsequent chromatographic separation resulted in the isolation of two novel diarylheptanoids, known as alnuside C ( 2) and alnuside D ( 3), and three known compounds, 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptan-3(R)-O-β-D-glucopyranoside ( 1), oregonin ( 4) and hirsutanone ( 5). The structures of the isolates were elucidated based on the use of extensive spectroscopic and chemical methods. Among the isolated diarylheptanoids, oregonin ( 4) (a major component of plant bark) and hirsutanone ( 5) exhibited potent in vitro inhibitory activity against T. brucei growth in the bloodstream with IC₅₀ values of 1.14 and 1.78 μM, respectively. We confirmed that oregonin ( 4) and hirsutanone ( 5) were not toxic to human normal skin fibroblast cells (NB1RGB) and colon cancer cells (HCT-15) at a concentration of 50 μM; however, lower levels of toxicity were observed for leukemia cells. To determine the structure activity relationships of the isolated components, we performed Conformation Search and found that the 3-oxo function of the heptane chain in the diarylheptanoid molecule is required for their trypanocidal activity. [ABSTRACT FROM AUTHOR]