ABSTRACT
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.
Subject(s)
Antiparasitic Agents/pharmacology , Benzoates/pharmacology , Piper/chemistry , Antiparasitic Agents/chemistry , Antiparasitic Agents/isolation & purification , Benzoates/chemistry , Benzoates/isolation & purification , Chromatography, Liquid , Magnetic Resonance Spectroscopy , Plant Leaves/chemistry , Species Specificity , Spectrometry, Mass, Electrospray IonizationABSTRACT
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 microg/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 microg/mL, respectively.
Subject(s)
Antiparasitic Agents/isolation & purification , Antiparasitic Agents/pharmacology , Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Benzoates/isolation & purification , Benzoates/pharmacology , Piper/chemistry , Plants, Medicinal/chemistry , Animals , Antimalarials , Antiparasitic Agents/chemistry , Antiprotozoal Agents/chemistry , Benzoates/chemistry , Bolivia , Leishmania/drug effects , Molecular Structure , Parasitic Sensitivity Tests , Plant Leaves/chemistry , Plasmodium falciparum/drug effects , Trypanosoma cruzi/drug effectsABSTRACT
A number of aminoalcohols, diamines and other related cycloanalogues of sphingosine have been synthesized and assayed in vitro against three Leishmania spp. and Trypanosoma cruzi. Most of the compounds were potent parasiticides, with IC50 values in the microM or lower range and potencies higher than those of pentamidine and benznidazol, the common therapeutic agents against these parasitoses.
Subject(s)
Cyclohexanols/pharmacology , Leishmania/drug effects , Sphingosine/analogs & derivatives , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Animals , Cyclohexanes/chemical synthesis , Cyclohexanes/chemistry , Cyclohexanes/pharmacology , Cyclohexanols/chemical synthesis , Cyclohexanols/chemistry , Diamines/chemical synthesis , Diamines/chemistry , Diamines/pharmacology , Inhibitory Concentration 50 , Sphingosine/pharmacology , Structure-Activity Relationship , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistryABSTRACT
Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25 microg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=10 and 16, respectively). The extracts from Desmopsis panamensis, Pseudomalmea boyacana, Rollinia exsucca and Rollinia pittieri showed good antiplasmodial activity (IC50 < 10 microg/ml). No correlation between antiplasmodial activity and inhibition of beta-hematin production was found. The present study gives specific and useful information about antiprotozoal and cytotoxic activities of some Annonaceae extracts. Results presented here also demonstrate which plants and/or plant parts could be useful in the treatment of leishmaniasis, Chagas' disease and malaria.
Subject(s)
Annonaceae , Antineoplastic Agents/pharmacology , Antiprotozoal Agents/pharmacology , Plant Extracts/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Antiprotozoal Agents/administration & dosage , Chloroquine , Colombia , Dose-Response Relationship, Drug , Drug Resistance , Humans , Inhibitory Concentration 50 , Leishmania/drug effects , Lethal Dose 50 , Medicine, Traditional , Phytotherapy , Plant Extracts/administration & dosage , Plants, Medicinal , Plasmodium falciparum/drug effects , Trypanosoma cruzi/drug effects , U937 CellsABSTRACT
El presente trabajo fue realizado con el objeto de plantear la busqueda de nuevos agentes tripanocidas de origen sintetico a travez de pruebas biologicas. Para la realizacion del mismo se utilizaron productos sinteticos derivados del acido isonotholaenico dihidroestibenoide natural, cuyos estudios forman parte del proyecto X5 Busqueda, Obtencion y evaluacion de nuevos agentes Antiparasitarios, en colaboracion con el CYTED "Ciencia y Tecnologia para el Desarollo. La evaluacion fue realizada in vitro, en cultivo de formas epimastigotes (Tulahuen CI-Brener) y tripanigotes de Trypanpsoma cruzi (cepa Y). Se reportaron actividades antichagasica de varios de estos derivados como compuestos representativos y relacionados con series sinteticas comoestructuras basicas de benzaldehidos dihidroestilbamidas, isoindoles. 1-talazina,imidazol (2.1 a)isoindoles y pirimida (2.2-a)isoindoles. Algunos compuestos evaluados resultaron ser potentes como el benznidazol droga control (epimastigotes) y otros mostraron ser mas activos que el Violeta de Genciana (tripomastigote), usada como droga de referencia. Delos 34 productos evaluados contra T. Cruzi (tripomastigotes) en vitro 2 porciento de estos mostraron actividad (1c50<13ug-ml)y un 50 porciento con actividad moderada con relacion a la droga de referencia Violeta de Genciana. Un derivado estilboneide dio actividad contra epimastigotes (tulahuen CL-Brener) IC50=10 UG/MLy un 75 porciento mostraron una actividad moderada en relacion al BENZNIDAZOL. De los dos productos encontrados activos se determino el tiempo de efctividad sometiendo a cultivos in vitro a diferentes temperaturas y a distintos tiempos, observando un 80 porciento de inhibicion de la parasitemia a las dos horas y un a 100 porciento a las 24 horas