Benzoic acid derivatives from Piper species and their antiparasitic activity

Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3′-methyl-2′-butenyl)benzoate (7) exhibited leishmanicidal effect (IC₅₀ 13.8-18.5 μg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl) benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC₅₀ values of 16.4, 15.6, and 18.5 μg/mL, respectively.