Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.
Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5 microg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2 microg/ml) and trypanocidal (16.5 microg/ml) activities, respectively.
Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Avda. Astrofísico, Francisco Sánchez 2, La Laguna, 38206 Tenerife, Canary Islands, Spain.
Ninoska
N
Flores
Ignacio A
IA
Jiménez
Alberto
A
Giménez
Grace
G
Ruiz
David
D
Gutiérrez
Genevieve
G
Bourdy
Isabel L
IL
Bazzocchi
D000977:Antiparasitic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002853:Chromatography, Liquid; D009682:Magnetic Resonance Spectroscopy; D031701:Piper / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D013045:Species Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
D000977:Antiparasitic Agents; D001565:Benzoates