RESUMO
Leishmania mexicana (L. mexicana) is a causal agent of cutaneous leishmaniasis (CL), a "Neglected disease", for which the search for new drugs is a priority. Benzimidazole is a scaffold used to develop antiparasitic drugs; therefore, it is interesting molecule against L. mexicana. In this work, a ligand-based virtual screening (LBVS) of the ZINC15 database was performed. Subsequently, molecular docking was used to predict the compounds with potential binding at the dimer interface of triosephosphate isomerase (TIM) of L. mexicana (LmTIM). Compounds were selected on binding patterns, cost, and commercial availability for in vitro assays against L. mexicana blood promastigotes. The compounds were analyzed by molecular dynamics simulation on LmTIM and its homologous human TIM. Finally, the physicochemical and pharmacokinetic properties were determined in silico. A total of 175 molecules with docking scores between -10.8 and -9.0 Kcal/mol were obtained. Compound E2 showed the best leishmanicidal activity (IC50 = 4.04 µM) with a value similar to the reference drug pentamidine (IC50 = 2.23 µM). Molecular dynamics analysis predicted low affinity for human TIM. Furthermore, the pharmacokinetic and toxicological properties of the compounds were suitable for developing new leishmanicidal agents.
RESUMO
In this study, the antifungal, biosurfactant and bioemulsifying activity of the lipopeptides produced by the marine bacterium Bacillus subtilis subsp. spizizenii MC6B-22 is presented. The kinetics showed that at 84 h, the highest yield of lipopeptides (556 mg/mL) with antifungal, biosurfactant, bioemulsifying and hemolytic activity was detected, finding a relationship with the sporulation of the bacteria. Based on the hemolytic activity, bio-guided purification methods were used to obtain the lipopeptide. By TLC, HPLC and MALDI-TOF, the mycosubtilin was identified as the main lipopeptide, and it was further confirmed by NRPS gene clusters prediction based on the strain's genome sequence, in addition to other genes related to antimicrobial activity. The lipopeptide showed a broad-spectrum activity against ten phytopathogens of tropical crops at a minimum inhibitory concentration of 400 to 25 µg/mL and with a fungicidal mode of action. In addition, it exhibited that biosurfactant and bioemulsifying activities remain stable over a wide range of salinity and pH and it can emulsify different hydrophobic substrates. These results demonstrate the potential of the MC6B-22 strain as a biocontrol agent for agriculture and its application in bioremediation and other biotechnological fields.
RESUMO
Trypanosomatids are the causative agents of leishmaniasis and trypanosomiasis, which affect about 20 million people in the world's poorest countries, leading to 95,000 deaths per year. They are often associated with malnutrition, weak immune systems, low quality housing, and population migration. They are generally recognized as neglected tropical diseases. New drugs against these parasitic protozoa are urgently needed to counteract drug resistance, toxicity, and the high cost of commercially available drugs. Microbial bioprospecting for new molecules may play a crucial role in developing a new generation of antiparasitic drugs. This article reviews the current state of the available literature on chemically defined metabolites of microbial origin that have demonstrated antitrypanosomatid activity. In this review, bacterial and fungal metabolites are presented; they originate from a range of microorganisms, including cyanobacteria, heterotrophic bacteria, and filamentous fungi. We hope to provide a useful overview for future research to identify hits that may become the lead compounds needed to accelerate the discovery of new drugs against trypanosomatids.
Assuntos
Antiprotozoários/uso terapêutico , Bactérias/química , Fungos/química , Leishmaniose/tratamento farmacológico , Trypanosomatina/fisiologia , Tripanossomíase/tratamento farmacológico , Animais , Humanos , Leishmaniose/metabolismo , Tripanossomíase/metabolismoRESUMO
Culex quinquefasciatus Say (Diptera: Culicidae), an arboviral and filarial vector, is one of the most widespread mosquitoes in the world. The indiscriminate use of synthetic chemical insecticides has led to the development of resistance in mosquito populations worldwide. The effect of continuous exposure to crude extracts of Argemone mexicana, the Mexican poppy, on the development and growth stages of second-instar larvae of the mosquito was studied, along with qualitative chemical analysis of the different plant parts. Inhibition, mortality, and larval and pupal duration phases were assessed. Second-instar mosquito larvae were exposed to crude ethanol extracts of flowers, stems, and seeds. Flower extract exhibited the strongest larvicidal activity with LC50 and LC90 values after 24 h of exposure of 18.61 and 39.86 ppm, respectively, and 9.47 and 21.76 ppm after 48 h. Extracts from stem and seeds were significantly less effective. The flower extract registered a Growth Inhibition Index of 0.01 at 25 ppm, with stems and seeds registering 0.05 and 0.08, respectively, at 100 ppm (control group 1.02). Qualitative chemical analysis by thin-layer chromatography showed characteristic spots indicating the presence of alkaloids and flavonoids and phytochemical screening showed the presence of alkaloids, anthraquinones, flavonoids, tannins, and terpenoids in the various crude extracts. This is the first report of the effectiveness of an ethanol flower extract of A. mexicana on Cx. quinquefasciatus; it can be considered a promising alternative control for this mosquito species.
Assuntos
Argemone , Culex , Controle de Mosquitos , Extratos Vegetais , Animais , Feminino , Larva , Testes de ToxicidadeRESUMO
Cadmium is a major heavy metal found in polluted aquatic environments, mainly derived from industrial production processes. We evaluated the biosorption of solubilized Cd2+ using the extracellular polymeric substances (EPS) produced by Bacillus sp. MC3B-22 and Microbacterium sp. MC3B-10 (Microbactan); these bacteria were originally isolated from intertidal biofilms off the coast of Campeche, Mexico. EPS were incubated with different concentrations of cadmium in ultrapure water. Residual Cd2+ concentrations were determined by Inductive Coupled Plasma-Optic Emission Spectrometry and the maximum sorption capacity (Qmax) was calculated according to the Langmuir model. EPS were characterized by X-ray photoelectron spectroscopy (XPS) before and after sorption. The Qmax of Cd2+ was 97 mg g-1 for Microbactan and 141 mg g-1 for MC3B-22 EPS, these adsorption levels being significantly higher than previously reported for other microbial EPS. In addition, XPS analysis revealed changes in structure of EPS after biosorption and showed that amino functional groups contributed to the binding of Cd2+, unlike other studies that show the carbohydrate fraction is responsible for this activity. This work expands the current view of bacterial species capable of synthesizing EPS with biosorbent potential for cadmium and provides evidence that different chemical moieties, other than carbohydrates, participate in this process.
Assuntos
Biopolímeros/química , Cádmio/química , Poluentes Químicos da Água/química , Actinobacteria/metabolismo , Adsorção , Bacillus/metabolismo , Biofilmes , Biopolímeros/metabolismo , MéxicoRESUMO
We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis. In particular, compound 4 (an indomethacin hybrid) was one of the most potent of the series, inhibiting G. intestinalis growth in vitro with an IC50 of 0.145µM. Compound 4 was 38-times more potent than metronidazole and 8-times more active than nitazoxanide. The in vivo giardicidal effect of 4 was evaluated in a CD-1 mouse model obtaining a median effective dose of 1.709µg/kg (3.53nmol/kg), a 321-fold and 1015-fold increase in effectiveness after intragastric administration over metronidazole and nitazoxanide, respectively. Compounds 1 and 3 (hybrids of ibuprofen and clofibric acid), showed potent giardicidal activities in the in vitro as well as in the in vivo assays after oral administration. Therefore, compounds 1-5 constitute promising drug candidates for further testing in experimental chemotherapy against giardiasis, trichomoniasis, leishmaniasis and even trypanosomiasis infections.
Assuntos
Antiprotozoários/química , Antiprotozoários/uso terapêutico , Giardia lamblia/efeitos dos fármacos , Giardíase/tratamento farmacológico , Tiazóis/química , Tiazóis/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Desenho de Fármacos , Feminino , Humanos , Leishmania/efeitos dos fármacos , Camundongos , Nitrocompostos , Infecções por Protozoários/tratamento farmacológico , Tiazóis/síntese química , Tiazóis/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Soil and rock surfaces support microbial communities involved in mineral weathering processes. Using selective isolation, fungi were obtained from limestone surfaces of Mayan monuments in the semi-arid climate at Yucatan, Mexico. A total of 101 isolates representing 53 different taxa were studied. Common fungi such as Fusarium, Pestalotiopsis, Trichoderma, and Penicillium were associated with surfaces and were, probably derived from airborne spores. In contrast, unusual fungi such as Rosellinia, Annulohypoxylon, and Xylaria were predominantly identified from mycelium particles of biofilm biomass. Simulating oligotrophic conditions, agar amended with CaCO3 was inoculated with fungi to test for carbonate activity. A substantial proportion of fungi, in particular those isolated from mycelium (59%), were capable of solubilizing calcium by means of organic acid release, notably oxalic acid as evidenced by ion chromatography. Contrary to our hypothesis, nutrient level was not a variable influencing the CaCO3 solubilization ability among isolates. Particularly active fungi (Annulohypoxylon stygium, Penicillium oxalicum, and Rosellinia sp.) were selected as models for bioweathering experiments with limestone-containing mesocosms to identify if other mineral phases, in addition to oxalates, were linked to bioweathering processes. Fungal biofilms were seen heavily covering the stone surface, while a biomineralized front was also observed at the stone-biofilm interface, where network of hyphae and mycogenic crystals was observed. X-ray diffraction analysis (XRD) identified calcite as the main phase, along with whewellite and wedellite. In addition, lower levels of citrate were detected by Attenuated Total Reflectance-Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Overall, our results suggest that a diverse fungal community is associated with limestone surfaces insemi-arid climates. A subset of this community is geochemically active, excreting organic acids under quasi-oligotrophic conditions, suggesting that the high metabolic cost of exuding organic acids beneficial under nutrient limitation. Oxalic acid release may deteriorate or stabilize limestone surfaces, depending on microclimatic dynamics.
RESUMO
This work describes the use of Colubrina greggii as a model to investigate the use of chemometric analysis combined with data from a leishmanicidal bioassay, using Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures (O-PLS), to detect biologically active natural products in crude extracts from plants having little or no phytochemical information. A first analysis of the HPLC-UV profiles of the extract and its semi-purified fractions using both Principal Component Analysis (PCA) and Orthogonal Partial Least Squares (O-PLS) indicated that the components at tR 48.2, 48.7, 51.8min correlated with the variation in bioactivity. However, a further O-PLS analysis of the HPLC-UV profiles of fractions obtained through a final semi-preparative HPLC purification showed two components at tR 48.7 and 49.5min which correlated with the variation of the bioactivity in a high performance predictive model, with high determination coefficient, high correlation coefficient values (R(2) and Q(2)=0.99) and a low root mean square error (RMSE=0.018). This study demonstrates that the association of chemometric analysis with bioassay results can be an excellent strategy for the detection and isolation of bioactive metabolites from phytochemically unknown plant crude extracts.
Assuntos
Compostos Fitoquímicos/metabolismo , Extratos Vegetais/metabolismo , Antiparasitários/isolamento & purificação , Antiparasitários/metabolismo , Antiparasitários/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Colubrina/química , Colubrina/metabolismo , Misturas Complexas , Análise dos Mínimos Quadrados , Leishmania mexicana/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais , Análise de Componente Principal , Raios UltravioletaRESUMO
The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50=10nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed an excellent leishmanicidal and trypanocidal effect, repurposing this drug as potential new antikinetoplastid parasite compound.
Assuntos
Antiprotozoários/farmacologia , Infecções por Protozoários/imunologia , Tiazóis/química , Animais , Desenho de Fármacos , HumanosRESUMO
A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan is a high molecular weight (700 kDa), non-ionic molecule. Gas chromatography of the lipid fraction revealed the presence of palmitic, stearic, and oleic acids; thus microbactan may be considered a glycolipoprotein. Microbactan emulsified aromatic hydrocarbons and oils to various extents; the highest emulsification index was recorded against motor oil (96%). The stability of the microbactan-motor oil emulsion model reached its highest level (94%) at 50 °C, pH 10 and 3.5% NaCl content. It was not toxic to Artemia salina nauplii. Microbactan is, therefore, a non-toxic and non-ionic bioemulsifier of high molecular weight with affinity for a range of oily substrates. Comparative phylogenetic assessment of the 16S rDNA gene of Microbacterium sp. MC3B-10 with genes derived from other marine Microbacterium species suggested that this genus is well represented in coastal zones. The chemical nature and stability of the bioemulsifier suggest its potential application in bioremediation of marine environments and in cosmetics.
Assuntos
Actinomycetales/metabolismo , Emulsificantes/metabolismo , Actinomycetales/classificação , Animais , Artemia/efeitos dos fármacos , Biodegradação Ambiental , Emulsificantes/química , Emulsificantes/toxicidade , Hidrocarbonetos Aromáticos/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Óleos/química , Ácido Oleico/química , Ácido Palmítico/química , Filogenia , Ácidos Esteáricos/química , TemperaturaRESUMO
A total of 82 fungal extracts were selected and screened against Mycobacterium tuberculosis and promastigotes of Leishmania mexicana strains. Results showed inhibitory activity in 29 % of the fungal strains against at least one of the targets tested. The most significant antituberculosis (antiTB) effects were presented by Cylindrocarpon sp. XH9B, Fusarium sp. TA54, Fusarium XH1Ga, Gliocladium penicillioides TH04 and TH21, Gliocladium sp. TH16, Kutilakesa sp. MR46, and Verticillium sp. TH28 strains (minimal inhibition concentration (MIC) = 1.56-25 µg/ml). Mortality of L. mexicana promastigotes was displayed by only four strains, Fusarium sp. TA50, Fusarium sp. TA54, Verticillium sp. TH28, and the unidentified 2TA2 strain (IC(50) = 14.23-100 µg/ml and IC(100) = 50-100 µg/ml). Seven of these most active strains were defatted and their corresponding fractions evaluated again. The results showed the best antiTB activity in Gliocladium sp. TH16 (MIC = 1.56 µg/ml) and the highest leishmanicidal potential in Fusarium sp. TA54 (IC(50) = 6.36 µg/ml). These results show that fungi living in the tropical regions of México have the ability to produce bioactive metabolites that could be used in the near future as natural products to control neglected tropical diseases.
Assuntos
Antiprotozoários/farmacologia , Antituberculosos/farmacologia , Fungos/química , Leishmania mexicana/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Antiprotozoários/isolamento & purificação , Antituberculosos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , México , Testes de Sensibilidade Microbiana , Clima TropicalRESUMO
The bioassay-guided phytochemical investigation of the leaf extract of Serjania yucatanensis, a woody climbing plant endemic to the Yucatan peninsula, led to the identification of a mixture of a triterpene [lup-20(29)-en-3-one] and an oxygenated sesquiterpene (ß-caryophyllene oxide), as that responsible for the originally detected trypanocidal activity in the organic crude extract. Results showed that the mixture of lup-20(29)-en-3-one and ß-caryophyllene oxide is active against trypomastigotes of Trypanosoma cruzi (IC(50) =80.3 µg/mL) and inhibits the egress of trypomastigotes from infected Vero cells (when tested at 100 µg/mL) without being cytotoxic.
Assuntos
Antiprotozoários/farmacologia , Extratos Vegetais/farmacologia , Sapindaceae/química , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Bioensaio , Chlorocebus aethiops , Concentração Inibidora 50 , Testes de Sensibilidade Parasitária , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Sesquiterpenos/análise , Sesquiterpenos/farmacologia , Triterpenos/análise , Triterpenos/farmacologia , Células VeroRESUMO
Ethanol extracts of Senna villosa, Serjania yucatanensis, Byrsonima bucidaefolia, and Bourreria pulchra were evaluated for their in vitro activity against epimastigotes and trypomastigotes of Trypanosoma cruzi. Results showed that the leaf extracts of S. yucatanensis and B. pulchra were the most active against epimastigotes (IC(100) = 100 µg/mL) and trypomastigotes of T. cruzi (95% or more reduction in the number of parasites at 100 and 50 µg/mL). However, only the leaf extract of S. yucatanensis showed significant trypanocidal activity when tested in vivo, reducing 75% of the parasitemia in infected mice at 100 mg/kg. This same extract inhibited the egress of trypomastigotes from infected cells and proved not to be cytotoxic (IC(50) = 318.8 ± 2.3 µg/mL).
Assuntos
Antiprotozoários/administração & dosagem , Antiprotozoários/farmacologia , Gleiquênias/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/isolamento & purificação , Doença de Chagas/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Humanos , Concentração Inibidora 50 , México , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/tratamento farmacológico , Testes de Sensibilidade Parasitária , Extratos Vegetais/isolamento & purificação , Resultado do TratamentoRESUMO
We have synthesized two new benzologues of Nitazoxanide (NIT) and Tizoxanide (TIZ), using a short synthetic route. Both compounds were tested in vitro against six protozoa (Giardia intestinalis, Trichomonas vaginalis, Entamoeba histolytica, Plasmodium berghei, Leishmania mexicana and Trypanosoma cruzi). Compound 1 (benzologue of NIT) showed broad antiprotozoal effect against all parasites tested, showing IC(50)'s<5 µM. This compound was five-times more active than NIT, and 18-times more potent than metronidazole against G. intestinalis. It was 10-times more active than pentamidine against L. mexicana, and it was sevenfold more potent than benznidazole versus T. cruzi. This compound could be considered as a new broad spectrum antiprotozoal agent.
Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Tiazóis , Giardia/efeitos dos fármacos , Estrutura Molecular , Nitrocompostos , Plasmodium/efeitos dos fármacos , Tiazóis/síntese química , Tiazóis/farmacologia , Trichomonas vaginalis/efeitos dos fármacosRESUMO
We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent.
Assuntos
Antibacterianos/síntese química , Antiprotozoários/síntese química , Ureia/química , Ureia/farmacologia , Antibacterianos/farmacologia , Antiprotozoários/farmacologia , Desenho de Fármacos , Giardia lamblia/efeitos dos fármacos , Humanos , Leishmania mexicana/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Quinolinas/síntese química , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade , Ureia/síntese químicaRESUMO
Microbial communities are ubiquitous in marine intertidal environments. These communities, which grow preferentially as biofilms on natural and artificial surfaces, carry out key processes contributing to the functioning of coastal environments and providing valuable services to human society, including carbon cycling, primary productivity, trophic linkage, and transfer and removal of pollutants. In addition, their surface-associated life style greatly influences the integrity and performance of marine infrastructure and archaeological heritage materials. The fluctuating conditions of the intertidal zone make it an extreme environment to which intertidal biofilm organisms must adapt at varying levels. This requirement has probably favored the development and spread of specific microorganisms with particular physiological and metabolic processes. These organisms may have potential biotechnological utility, in that they may provide novel secondary metabolites, biopolymers, lipids, and enzymes and even processes for the production of energy in a sustainable manner.
Assuntos
Biologia Marinha/métodos , Biofilmes/crescimento & desenvolvimentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tridax procumbens is an active herb against leishmaniasis. AIM OF THE STUDY: Leishmaniasis is a group of diseases caused by Leishmania protozoa. We investigated the antileishmanial activity of Tridax procumbens extracts and a pure compound against promastigotes of Leishmania mexicana, the causative agent of cutaneous leishmaniasis in the New World. MATERIALS AND METHODS: Extracts and (3S)-16,17-didehydrofalcarinol (1) were obtained by chromatographic methods from Tridax procumbens, and the latter identified by spectroscopic analysis. The effect of these extracts and 1 on the growth inhibition of promastigotes of Leishmania mexicana was evaluated. In order to test the safety of extracts and 1, mammalian cells were treated with them, and cell viability was assessed using trypan blue and MTT. RESULTS: We demonstrated that extracts of Tridax procumbens and 1 showed a pronounced activity against Leishmania mexicana. The methanol extract inhibited promastigotes growth of Leishmania mexicana with a 50% inhibitory concentration (IC(50)) of 3 microg/ml, while oxylipin 1 exhibited the highest inhibition at IC(50)=0.478 microg/ml. CONCLUSIONS: In this study we report the biological activity of extracts and (3S)-16,17-didehydrofalcarinol (1), obtained from Tridax procumbens, on the promastigote form of Leishmania mexicana, with no effect upon mammalian cells.
Assuntos
Antiparasitários/farmacologia , Asteraceae , Álcoois Graxos/farmacologia , Leishmania mexicana/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antiparasitários/química , Antiparasitários/isolamento & purificação , Antiparasitários/uso terapêutico , Linhagem Celular , Cães , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/uso terapêutico , Humanos , Leishmaniose/parasitologia , Leucócitos Mononucleares/efeitos dos fármacos , Estágios do Ciclo de Vida , Estrutura Molecular , Testes de Sensibilidade Parasitária , Fitoterapia , Casca de Planta , Extratos Vegetais/química , Extratos Vegetais/uso terapêuticoRESUMO
Isocordoin (1) and 2',4'-dihydroxy-3'-(gamma,gamma-dimethylallyl)-dihydrochalcone (7), chalcones isolated from the root of Lonchocarpus xuul, together with six analogues of 1 were tested in vitro against promastigotes of Leishmania mexicana and epimastigotes of Trypanosoma cruzi. Additionally, cytotoxic studies with MDCK cells were carried out using the MTT method. Among these derivatives, 2',4'-diacetoxy-3'-(3-methylbut-2-enyl)-chalcone (2) and 2',4'-dimethoxy-3'-(3-methylbut-2-enyl)-chalcone (3) showed the strongest antiprotozoal activity and lower cytotoxicity in comparison with isocordoin at a concentration in the microM range. Derivative 3 had the strongest trypanocidal activity with IC(50) values lower than those of nifurtimox and benznidazole, the common drugs used against these parasites. The selectivity index calculated for 3 (SI 109.3) confirms the selective trypanocidal activity of this metabolite.
Assuntos
Antiprotozoários/farmacologia , Catecóis/farmacologia , Fabaceae/química , Leishmania mexicana/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Ascomicetos , Catecóis/química , Catecóis/isolamento & purificação , Linhagem Celular , Cães , Concentração Inibidora 50 , Extratos Vegetais/químicaRESUMO
Two unusual trinorsesquiterpenoids, urechitols A (1) and B (2), were isolated from the root extract of Pentalinon andrieuxii, a plant used commonly in Yucatecan traditional medicine to treat leishmaniasis. The structures of 1 and 2 were identified by interpretation of their spectroscopic data and chemical correlation reactions. The relative stereochemistry of 1 was confirmed through an X-ray crystallographic study.