ABSTRACT
Chagas' disease is caused by a parasitic protozoan and affects the poorest population in the world, causing high mortality and morbidity. As a result of the toxicity and long duration of current treatments, the discovery of novel and more efficacious drugs is crucial. In this work, the hexane extract from seeds of Porcelia macrocarpa R.E. Fries (Annonaceae) displayed in vitro antitrypanosomal activity against trypomastigote forms of T. cruzi by the colorimetric MTT assay (IC50 of 65.44 µg/mL). Using chromatographic fractionation over SiO2, this extract afforded a fraction composed by one active compound (IC50 of 10.70 µg/mL), which was chemically characterized as 12,14-octadecadiynoic acid (macrocarpic acid). Additionally, two new inactive acetylene compounds (α,α'-dimacro-carpoyl-ß-oleylglycerol and α-macrocarpoyl-α'-oleylglycerol) were also isolated from the hexane extract. The complete characterization of the isolated compounds was performed by analysis of NMR and MS data as well as preparation of derivatives.
Subject(s)
Acetylene/pharmacology , Annonaceae/chemistry , Fatty Acids/pharmacology , Plant Extracts/pharmacology , Seeds/chemistry , Trypanosoma cruzi/drug effects , Acetylene/chemistry , Chagas Disease/drug therapy , Fatty Acids/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Silicon Dioxide/chemistryABSTRACT
Parasitic protozoan diseases affect the poorest population in developing countries. Leishmaniasis and Chagas disease have been included among the most important threats for public health in Central and South American continent, with few therapeutic alternatives and highly toxic drugs. In the course of selection of novel drug candidates, we studied the anti-protozoal potential of Drimys brasiliensis. Thus, the crude hexane extract from stem bark as well as its main derivative, the sesquiterpene polygodial, were tested using in vitro assays. The crude hexane extract and polygodial showed activity against Leishmania spp. in the range between 22 and 62 µg/mL, but polygodial demonstrated high parasite selectivity towards Trypanosoma cruzi trypomastigotes (2 µg/mL), with a selectivity index of 19. Finally, polygodial showed a leishmanicidal effect, inducing intense ultrastructural damages in Leishmania in short-time incubation. The obtained results suggested that polygodial could be used as a tool for drug design studies against protozoan diseases and as a candidate molecule for further in vivo studies against T. cruzi.
