Abstract
Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC50 values < 20 mu g/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4 '-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4 ',7-dimethoxykaempferol, and naringenin 4 ',7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities <= 15 mu M. The most active compounds against T. brucei were naringenin 4 ',7 dimethyl ether and 4 ' methoxy kaempferol with activity of 15-20 mu M against the three T. brucei strains. The most active compounds against L. mexicana were 4 ',7-dimethoxykaempferol and the coumaric acid ester mixture, with EC50 values of 12.9 +/- 3.7 mu M and 13.1 +/- 1.0 mu M. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.