Apoprunellelactone (APL), an antiprotozoal lactone from the stem barks ofIsolona cooperiHutch. & Dalziel (Annonaceae)

Bioassay guided fractionation of the stem barks ofIsolona cooperiled to the isolation of a new lactone, apoprunellelactone (APL,1), and two known compounds, 5-[1-hydroxyhexyl]-2H-furan-2-one (2) and oleic acid (3). Their structures were elucidated by spectral analysis including MS, UV, IR, 1D and 2D-NMR spectroscopy. Evaluated for its antiprotozoal activities, APL (1) was found to be the most active onLeishmania donovaniandL. majorpromastigotes with EC(50)values of 16.3 and 8.2 mu M, respectively. AgainstTrypanosoma brucei bruceitrypomastigote forms, the activity of APL was moderated (MEC = 38.0 mu M). Its hemisynthetic ester acetic derivative (1c) was 2-42 times more active than that of the APL and reference drugs, justifying furtherin vivoevaluation of the two compounds (1and1c) onLeishmania spandTrypanosoma brucei brucei/mice models.