Dihydrochalcones and Benzoic Acid Derivatives from Piper dennisii

Two new dihydrochalcones ( 1, 2 ), as well as eight known compounds, piperaduncin C ( 3 ), 2′,6′-dihydroxy-4′-methoxydihydrochalcone ( 4 ), 4,2′,6′-trihydroxy-4′-methoxydihydrochalcone ( 5 ), 4-hydroxy-3,5-bis(3-methyl-2-butenyl)-benzoic acid ( 6 ), 3,5-bis(3-methyl-2-butenyl)-4-methoxybenzoic acid ( 7 ), 4-hydroxy-3-(3-methyl-2-butenoyl)-5-(3-methyl-2-butenyl)-benzoic acid ( 8 ), 2,2-dimethyl-8-(3-methyl-2-butenyl)-2 H -1-chromene-6-carboxylic acid ( 9 ), and 3-(3′,7′-dimethyl-2′,6′-octadienyl)-4-methoxybenzoic acid ( 10 ) were isolated from the leaves of Piper dennisii Trelease (Piperaceae), using a bioassay-guided fractionation to determine their antileishmanial potential. Among them, compound 10 exhibited the best antileishmanial activity (IC 50  = 20.8 µM) against axenic amastigote forms of Leishmania amazonensis , with low cytotoxicity on murine macrophages. In the intracellular macrophage-infected model, compound 10 proved to be more active (IC 50  = 4.2 µM). The chemical structures of compounds 1 – 10 were established based on the analysis of the spectroscopic data.