Context: 'Carnauba' wax is a natural product obtained from the processing of the powder exuded from Copernicia prunifera (Miller) H. E. Moore (Arecaceae). This material is widely used in the Brazilian folk medicine, including the treatment of rheumatism and syphilis. Objective: To investigate the antiprotozoal activity of hexane and EtOH extracts from the 'carnauba' wax as well as from the isolated compounds from the bioactive extracts. Material and methods: Two different samples of 'carnauba' (C. prunifera) waxes -types 1 and 4 -were individually extracted using hexane (EH) and EtOH (EE). Aliquots of hexane (type 1 -EH-1 and EH-4) and EtOH (type 4 -EE-1 and EE-4) extracts were tested against promastigote (2-200 lg/mL in DMSO during 48 h at 24 C) and amastigote (3-150 lg/mL in DMSO during 120 h at 37 C) forms of Leishmania infantum as well as against trypomastigote (3-150 lg/mL in DMSO during 24 h at 37 C) forms of Trypanosoma cruzi. Bioactive extracts EH-1 and EE-4 were subjected to a bioactivity-guided fractionation to afford three dammarane-type triterpenoids (1-3). The in vitro antiprotozoal activities of the obtained compounds were evaluated as described above. Additionally, the cytotoxicity activity of compounds 1-3 against mammalian conjunctive cells (NCTC -2-200 lg/mL in DMSO during 48 h at 37 C) was determined. Results: From the bioactive hexane and EtOH extracts from the 'carnauba' (C. prunifera) wax, were isolated three dammarane-type triterpenoids: (24R Ã )-methyldammar-25-ene-3b,20-diol (carnaubadiol, 1), (24R Ã )-methyldammara-20,25-dien-3-one (2) and (24R Ã )-methyldammara-20,25-dien-3a-ol (3). These compounds were identified based on the analysis of NMR and MS spectroscopic data. Compounds 1-3 were effective against the intracellular amastigotes of L. infantum, with IC 50 values ranging from 8 to 52 lM, while compounds 1 and 3 displayed activity against trypomastigote forms of T. cruzi with IC 50 values of 15 and 35 lM, respectively. The mammalian cytotoxicity assay demonstrated no damage to NCTC conjunctive cells up to 200 lM, except for compound 1, which demonstrated a CC 50 value of 34 lM. Conclusion: Based on the results, it was possible to conclude that the detected antiprotozoal bioactivity of 'carnauba' (C. prunifera) wax extracts could be related to the presence of the natural dammarane triterpenoid derivatives. The results suggested that these compounds could be used as promising scaffolds for drug design studies for leishmaniasis and Chagas disease. ARTICLE HISTORY
BackgroundMajor drawbacks of the available treatment against Chagas disease (American trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. Therefore, the discovery of alternative drugs for treating chronic Chagas disease requires immediate action. In this work, we evaluated the mushroom Pleurotus salmoneostramineus in the search for potential antiparasitic compounds.MethodsFruit bodies of the basidiomycete Pleurotus salmoneostramineus were triturated and submitted to organic solvent extraction. After liquid-liquid partition of the crude extract, three fractions were obtained and the bioguided fractionation study was conducted to isolate the active metabolites. The elucidation of the chemical structure was performed using GC-MS and NMR techniques. The biological assays for antiparasitic activity were carried out using trypomastigotes of Trypanosoma cruzi and murine macrophages for mammalian cytotoxicity. The mechanism of action of the isolated compound used different fluorescent probes to evaluate the plasma membrane permeability, the potential of the mitochondrial membrane and the intracellular levels of reactive oxygen species (ROS).ResultsThe most abundant fraction showing the antiparasitic activity was isolated and chemically elucidated, confirming the presence of ergosterol. It showed anti-Trypanosoma cruzi activity against trypomastigotes, with an IC50 value of 51.3 μg/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 μg/mL. The mechanism of action of ergosterol in Trypanosoma cruzi trypomastigotes resulted in permeabilization of the plasma membrane, as well as depolarization of mitochondrial membrane potential, leading to parasite death. Nevertheless, no increase in ROS levels could be observed, suggesting damages to plasma membrane rather than an induction of oxidative stress in the parasite.ConclusionsThe selection of naturally antiparasitic secondary metabolites in basidiomycetes, such as ergosterol, may provide potential scaffolds for drug design studies against neglected diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-017-0120-0) contains supplementary material, which is available to authorized users.
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- OPEN ACCESSMolecules 2015, 20 8169 carpoyl-β-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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.