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This study highlights Adesmia pinifolia, a native high-Andean species, as a potential candidate for the phytoremediation of soils contaminated with Cd and Hg. In this work, a semi-hydronic assay with different doses of Cd (3, 4.5, and 6 mg L-1) and Hg (0.8, 1.2, and 1.6 mg L-1) was analysed to evaluate the establishment of plants, antioxidant defence systems, oxidative stress, and the ability to accumulate heavy metals. The results indicate high survival rates (>80%); however, Cd significantly reduced shoot and root biomass, while Hg increased root biomass with the 1.6 mg L-1 treatment. Cd and Hg tend to accumulate more in roots (2534.24 µg/g and 596.4 µg g-1, respectively) compared to shoots (398.53 µg g-1 and 140.8 µg g-1, respectively). A significant decrease in the bioconcentration factor of Cd and Hg in roots was observed as metal levels increased, reaching the maximum value at 3 mg L-1 (805.59 ± 54.38) and 0.8 mg L-1 (804.54 ± 38.09). The translocation factor, <1 for both metals, suggests that translocation from roots to shoots is limited. An overproduction of reactive oxygen species (ROS) was observed, causing lipid peroxidation and oxidative damage to plant membranes. Tolerance strategies against subsequent toxicity indicate that enhanced glutathione reductase (GR) activity and glutathione (GSH) accumulation modulate Cd and Hg accumulation, toxicity, and tolerance.
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This study aimed to evaluate the in silico and in vitro inhibitory effect of the combined use of galantamine (GAL) and donepezil (DON) against acetylcholinesterase and butyrylcholinesterase (BuChE) enzymes. In silico and in vitro cholinesterase analysis were carried out for GAL and DON alone and combined. Molecular modeling studies were carried out (docking analysis, molecular dynamics simulation, and quantum theory of atoms in molecules). Cholinesterase's inhibitory activities by modified Ellman's method and the drug combination effect using the Chou-Talalay method were assayed. GAL/DON combination showed the co-occupancy of the ligands in both enzymes through in silico studies. Regarding in vitro BuChE inhibition analyses, three of five combinations showed an interaction between GAL and DON at the threshold of additive affect (0.9 < CI < 1.1), with a tendency toward a synergistic effect for higher concentrations. This is the first report showing the efficacy of the GAL/DON combinations inhibiting BuChE, showing the importance of analyzing the behavior of different ligands when co-occupancy into the active site is possible. These combinations might be a possible therapy to improved efficacy, reduced doses, minor side effects, and high levels of the neurotransmitter in the synaptic space for Alzheimer's disease.
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Doença de Alzheimer , Galantamina , Humanos , Galantamina/farmacologia , Butirilcolinesterase/metabolismo , Donepezila/farmacologia , Inibidores da Colinesterase/farmacologia , Acetilcolinesterase/metabolismo , Relação Estrutura-Atividade , Doença de Alzheimer/tratamento farmacológico , Simulação de Acoplamento MolecularRESUMO
Microbial contamination remains a significant economic challenge in the food industry, emphasizing the need for innovative antimicrobial solutions. In this study, we synthesized N-sulfonyl-1,2,3,4-tetrahydroisoquinolines (NSTHIQ) derivatives using an environmentally friendly Preyssler heteropolyacid catalyst, obtaining moderate to high yields (35-91 %) under mild conditions. Two derivatives (5 and 6) exhibited significant antifungal properties against various fungal species, including Aspergillus spp, Penicillium spp, and Botrytis cinerea. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis revealed the absence of hepatic toxicity in all compounds, making derivatives 2, 3, 4, and 5 potential candidates for further development. However, derivatives 6 and 7 exhibited immunotoxicity. In support of our experimental findings, reactivity indices were computed using Density Functional Theory principles, deriving valuable insights into the chemical properties of these derivatives. This study underscores the potential of NSTHIQ compounds as potent antifungal agents, coupled with the importance of employing environmentally friendly catalysts in drug discovery.
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Anti-Infecciosos , Tetra-Hidroisoquinolinas , Testes de Sensibilidade Microbiana , Anti-Infecciosos/química , Antifúngicos/farmacologia , Antifúngicos/química , Aspergillus , Tetra-Hidroisoquinolinas/farmacologia , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, represents a health threat to around 20 million people worldwide. Side effects of benznidazole (Bzn) cause 15-20% of patients to discontinue their treatment. Evidence has increased in favor of the use of drug combinations to improve the efficacy and tolerance of the treatment. Natural products are well known to provide structures that could serve as new drugs or scaffolds for CD treatment. Spp of the Amaryllidoideae sub family of Amaryllidaceae family are known by their bioactives alkaloids, which have been reported by their antiparasitic activities. PURPOSE: To evaluate the anti-T. cruzi activity of the isolated alkaloid candimine (Cnd) from Hippeastrum escoipense Slanis & Huaylla; and to assess the combination effect between Cnd and Bzn against different life stages of T. cruzi parasites. METHODS: The chemical profile of H. escoipense alkaloids extract (AE-H. escoipense), including quantitation of Cnd was performed through GC/MS and UPLC-MS/MS techniques. Subsequently, Cnd was isolated using Shephadex LH-20. Then, the AE-H. escoipense and Cnd were tested against T. cruzi, (epimastigotes, trypomastigotes, and amastigotes) by in vitro proliferation and viability assays. The cytotoxicity was evaluated against Vero and HepG2 mammalian cells. The ultrastructural analysis was perform by transmission electron microscopy (TEM) and mitochondrial activity was carried out by MTT assay. Drug combination assay between Cnd and Bzn was evaluated using the Chou-Talalay method. RESULTS: The AE-H. escoipense and Cnd showed high and specific anti-T. cruzi activity, comparable to Bzn. Cnd induces ultrastructural changes in T. cruzi, such as vacuolization, membrane blebs, and increased mitochondrial activity. Regarding the interaction between Cnd and Bzn, it generates synergism in the combinations of 0.25×IC50 in epimastigotes, 2×IC50 in trypomastigotes+amastigotes, and 0.25, 2, and 4×IC50 in amastigotes. CONCLUSION: The synergism between Cnd and Bzn indicates that the combination at the concentration of 4×IC50 could be useful as an effective new therapy against CD in the chronic stage. Thus, Cnd isolated from the leaves of H. escoipense emerges as potential candidate for the development of a new drug for the treatment of CD.
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Alcaloides , Amaryllidaceae , Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Animais , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Doença de Chagas/tratamento farmacológico , Alcaloides/farmacologia , Tripanossomicidas/farmacologia , MamíferosRESUMO
BACKGROUND: Hippeastrum species have a wide range of biological properties. In Argentina, this genus comprises ten widely distributed species. PURPOSE: To evaluate the antiparasitic and anticholinesterase activities and chemical profiles of seven Argentinean Hippeastrum species and determine the synergism between the major isolated alkaloid-montanine-and benznidazole in anti-Trypanosoma cruzi activity. METHODS: The antiparasitic activity was evaluated through antiproliferative and viability assays against T. cruzi epimastigotes. Synergism assays were performed using the Chou-Talalay method. AChE and BuChE inhibitory activities were also assessed. The alkaloid composition was obtained using GC-MS analysis. RESULTS: All extracts showed strong growth inhibition of T. cruzi epimastigote proliferation. The extracts from H. aglaiae, H. aulicum, and H. hybrid stand out for their potent and total growth inhibition, which was comparable to benznidazole. The H. reticulatum extract showed strong Acetylcholinesterase (AChE) inhibitory activities, while five species showed moderate Butyrylcholinesterase (BuChE) inhibition. Fifteen alkaloids were identified by means of GC-MS. Regarding the synergism assessment, the highest synergistic effect was obtained from the combination of montanine and benznidazole. CONCLUSION: Hippeastrum species bulb extracts from Argentina were shown to be a good source of antiparasitic alkaloids and cholinesterase inhibitors. The synergism between montanine and benznidazole emerges as a potential combination for future studies to treat Chagas disease.
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BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, affects over six million people worldwide, mainly in Latin American countries. Currently available drugs have variable efficacy in the chronic phase and significant side effects, so there is an urgent need for safer chemotherapeutic treatments. Natural products provide privileged structures that could serve as templates for the synthesis of new drugs. Among them, Amaryllidaceae plants have proved to be a potential natural source of therapeutical agents due to their rich diversity in alkaloids. PURPOSE: To identify alkaloids with anti-T. cruzi activity from Habranthus brachyandrus (Baker) Sealy (Amaryllidaceae, subfamily Amaryllidoideae) collected in Argentina. METHODS: An H. brachyandrus alkaloid extract was tested against T. cruzi, and its cytotoxicity profile was evaluated against two mammalian cell lines to ascertain its selectivity against the parasite and potential liver toxicity. It was also assessed by a stage-specific anti-amastigote assay and analysed by GC/MS to determine its alkaloid profile. The isolated alkaloids were also tested using the aforementioned assays. RESULTS: The extract showed high and specific activity against T. cruzi. The alkaloids lycoramine, galanthindole, 8-O-demethylmaritidine, 8-O-demethylhomolycorine, nerinine, trisphaeridine, deoxytazettine, and tazettamide were identified by means of GC-MS. In addition, hippeastidine (also named aulicine), tazzetine, ismine, and 3-epimacronine were isolated. The alkaloid ismine was specifically active against the parasite and had low toxicity against HepG2 cells, but did not show anti-amastigote activity. CONCLUSION: The extract had specific anti-T. cruzi activity and the isolated alkaloid ismine was partially responsible of it. These results encourage further exploration of H. brachyandrus alkaloids in search of novel starting points for Chagas disease drug development.
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Alcaloides , Alcaloides de Amaryllidaceae , Amaryllidaceae , Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Alcaloides/uso terapêutico , Amaryllidaceae/química , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Animais , Argentina , Doença de Chagas/tratamento farmacológico , Humanos , Mamíferos , Extratos Vegetais/química , Tripanossomicidas/química , Tripanossomicidas/farmacologiaRESUMO
Triadimefon (TDM) and cyproconazole (CPZ) are two triazoles widely used as fungicides. Several azoles were synthesised starting from commercial TDM and CPZ. The compounds were evaluated against phytopathogenic filamentous fungi, including Aspergillus fumigatus (AF), A. niger (AN), A. ustus (AU), A. japonicus (AJ), A. terreus (AT), Fusarium oxysporum and Botrytis cinerea isolated from grapevine in the province of San Juan, Argentina. Three of the synthesised compounds (1-(Biphenyl-4-yloxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one, 1; 2-(Biphenyl-4-yl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, 3; 3-Cyclopropyl-2-(4'-fluorobiphenyl-4-yl)-1-(1H-1,2,4-triazol1-yl)butan-2-ol, 4) presented remarkable in vitro fungicidal properties, with better effects than TDM and CPZ on some of the target fungi. Cytotoxicity was assessed using human lung fibroblasts MRC5. Derivative 1, with IC50 values of 389.4 µM, was less toxic towards MRC-5 human lung fibroblasts than commercial TDM (248.5 µM) and CPZ (267.4 µM). Docking analysis and molecular dynamics simulations suggest that the compounds present the same interaction in the binding pocket of the CYP51B enzyme and with the same amino acids as CPZ. The derivatives investigated could be considered broad-spectrum but with some selectivity towards imperfect fungi.
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Chronic high-fat diet consumption induces hypercholesterolemia. The effect of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) was studied on the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and triglycerides, and on the expression of liver X receptors (LXRs) in a hypercholesterolemic model. Adult male rats received a normal diet (ND) or a high-fat diet (HFD; normal diet + bovine fat + cholesterol). After 14 days, rats received water (W) or a decoction of the aerial parts of T. absinthioides (Ta; 10% w/v) for 2, 4, or 6 weeks. Four and six weeks of Ta improved the levels of TC and HDL-c in HFD. After 6 weeks of Ta, the expression of LXRs in HFD was the same as that in ND in both tissues. The Ta chemical profile was studied with an ultrahigh resolution liquid chromatography Orbitrap MS analysis (UHPLC-PDA-OT-MS/MS). Fifty-one compounds were identified, of which twelve are reported for the first time. Among these compounds, caffeoylquinic acid and its derivatives could modify the lipid profile and the expression of LXRs. This is the first in vivo report of T. absinthioides, which may be a potential candidate against hypercholesterolemia.
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We report a theoretical and experimental study on a new series of small-sized antibacterial peptides. Synthesis and bioassays for these peptides are reported here. In addition, we evaluated different physicochemical parameters that modulate antimicrobial activity (charge, secondary structure, amphipathicity, hydrophobicity and polarity). We also performed molecular dynamic simulations to assess the interaction between these peptides and their molecular target (the membrane). Biophysical characterization of the peptides was carried out with different techniques, such as circular dichroism (CD), linear dichroism (LD), infrared spectroscopy (IR), dynamic light scattering (DLS), fluorescence spectroscopy and TEM studies using model systems (liposomes) for mammalian and bacterial membranes. The results of this study allow us to draw important conclusions on three different aspects. Theoretical and experimental results indicate that small-sized peptides have a particular mechanism of action that is different to that of large peptides. These results provide additional support for a previously proposed four-step mechanism of action. The possible pharmacophoric requirement for these small-sized peptides is discussed. Furthermore, our results indicate that a net +4 charge is the adequate for 9 amino acid long peptides to produce antibacterial activity. The information reported here is very important for designing new antibacterial peptides with these structural characteristics.
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Antibacterianos/síntese química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Dicroísmo Circular , Interações Hidrofóbicas e Hidrofílicas , Estrutura Secundária de ProteínaRESUMO
This research was designed to investigate the metabolite profiling, phenolics and flavonoids content and the potential antioxidant, antibacterial and nematicidal activities of "yellow-brown resins" from Larrea divaricata Cav (LdRe) and L. nitida Cav (LnRe). Metabolite profiling was obtained using an ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP) and lipid peroxidation in erythrocytes (LP). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. In addition, the potential combinatory effect was analyzed with the fractional inhibitory concentration index (FICI) values using the checkerboard design. The nematicidal activity was carried out according to a standardized protocol. LdRe and LnRe showed a strong capture of the DPPH radical withvalues around 8.4 µg resin/mL; FRAP (1.69-1.94 mgTE/ g resin), TEAC (1.08-1.09 mgTE/g resin) and LP (81-82% at 100 µg of resin/mL) assays. A strong antimicrobial activity was displayed by both resins against methicillin-sensitive Staphylococcus aureus ATCC 25923(MSSA) and methicillin-resistant S. aureus ATCC 43300(MRSA) (MICs = 16-32 µg resin/mL). Additionally, the combination of LdRe or LnRe with the antibiotic cefotaxime showed an indifferent effect (FICI values = 1-1.25), however, this combinationcould be a potential strategy to reduce the drug doses, and in this way can be a potential alternative to reduce bacterial resistance. On the other hand, the resins showed a scarce nematicidal potential toward J2 Meloidogyne incognita; an important nematode infecting horticultural crops. Phenolics compounds were identified by UHPLC-PDA-OT-MS analysis, updating the knowledge on the chemical profile of these species. These results, together with the high content of quantified phenolics and flavonoids, allow the phenolics-enriched resins of these two Larrea species to be considered as a promising sustainable source of compounds of pharmacological interest.
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Plants in the Amaryllidaceae family synthesize a diversity of bioactive alkaloids. Some of these plant species are not abundant and have a low natural multiplication rate. The aims of this work were the alkaloids analysis of a Habranthus cardenasianus bulbs extract, the evaluation of its inhibitory activity against cholinesterases, and to test several propagation strategies for biomass production. Eleven compounds were characterized by GC-MS in the alkaloid extract, which showed a relatively high proportion of tazettine. The known alkaloids tazettine, haemanthamine, and the epimer mixture haemanthidine/6-epi-haemanthidine were isolated and identified by spectroscopic methods. Inhibitory cholinesterases activity was not detected. Three forms of propagation were performed: bulb propagation from seed, cut-induced bulb division, and micropropagated bulbs. Finally, different imbibition and post-collection times were evaluated in seed germination assays. The best propagation method was cut-induced bulb division with longitudinal cuts into quarters (T1) while the best conditions for seed germination were 0-day of post-collection and two days of imbibition. The alkaloids analyses of the H. cardenasianus bulbs showed that they are a source of anti-tumoral alkaloids, especially pretazettine (tazettine) and T1 is a sustainable strategy for its propagation and domestication to produce bioactive alkaloids.
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Alcaloides/análise , Alcaloides/farmacologia , Amaryllidaceae/química , Amaryllidaceae/crescimento & desenvolvimento , Inibidores da Colinesterase/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides de Amaryllidaceae/análise , Biomassa , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Cromatografia Gasosa-Espectrometria de Massas , Germinação , Estrutura Molecular , Fenantridinas/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Fatores de TempoRESUMO
This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential antioxidant and antibacterial, properties of orange-yellow resin from Zuccagnia punctata Cav (ZpRe). Metabolite profiling was obtained by a ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-ESI-OT-MS-MS). The antioxidant properties were screened by four methods: 2,2-diphenyl-1-picrylhydrazyl assay (DPPH), trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid peroxidation in erythrocytes (LP)). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) rules. The resin displayed a strong DPPH scavenging activity (IC50 = 25.72 µg/mL) and showed a percentage of inhibition of LP close to that of the reference compound catechin (70% at 100 µg ZpRe/mL), while a moderated effect was observed in the FRAP and TEAC assays. The resin showed a content of phenolic and flavonoid compounds of 391 mg GAE/g and 313 mg EQ/g respectively. Fifty phenolics compounds were identified by ultrahigh resolution liquid chromatography orbitrap MS analysis (UHPLC-PDA-OT-MS) analysis. Thirty-one compounds are reported for the first time, updating the knowledge on the chemical profile of this species. The importance of the biomolecules identified support traditional use of this endemic plant. Furthermore, additional pharmacological data is presented that increase the potential interest of this plant for industrial sustainable applications.
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The decoction of Tessaria absinthioides is used in traditional medicine of South America as hypocholesterolemic, balsamic, and expectorant; but it is also useful for the prevention of hepatitis, renal insufficiency, and diabetes, and is used as digestive. A lyophilized decoction from the aerial parts of this plant (TLD) collected in San Juan (TLDSJ) and Mendoza (TLDM) provinces (Argentina) and one collection from Antofagasta, Chile (TLDCH) were characterized regarding antioxidant and antibacterial activities, phenolics and flavonoids content, and ultrahigh resolution liquid chromatography Orbitrap MS analysis UHPLC-PDA-OT-MS/MS metabolite profiling. The antioxidant properties were carried out "in vitro" using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and trolox equivalent antioxidant activity (TEAC) methods, ferric-reducing antioxidant power (FRAP), and lipoperoxidation in erythrocytes (LP). The antibacterial activity was evaluated following the Clinical and Laboratory Standards Institute (CLSI) rules. TLDSJ, TLDM, and TLDCH displayed a strong DPPH scavenging activity (EC50 = 42, 41.6, and 43 µg/mL, respectively) and inhibition of lipoperoxidation in erythrocytes (86-88% at 250 µg TLD/mL), while a less effect in the FRAP and TEACantioxidant assays was found. Additionally, the decoctions showed a content of phenolics compounds of 94 mg gallic acid equivalents (GAE)/g, 185 GAE/g, and 64 GAE/g, for TLDSJ, TLDM, and TLDCH samples, respectively. Regarding the flavonoid content, the Chilean sample was highlighted with 19 mg quercetin equivalents (QE)/g. In this work, several phenolic compounds, including sesquiterpenes, flavonoids, and phenolic acids, were rapidly identified in TLDSJ, TLDM, and TLDCH extracts by means UHPLC-PDA-OT-MS/MS for the first time, which gave a first scientific support to consider this medicinal decoction from both countries as a valuable source of metabolites with antioxidant effects, some with outstanding potential to improve human health.
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The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC50 = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products.
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Antioxidantes/química , Baccharis/química , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão , Cinamatos/química , Flavonoides/química , Células HCT116 , Humanos , Peroxidação de Lipídeos , Espectrometria de Massas , Picratos/químicaRESUMO
BACKGROUND: Embelin (EMB), obtained from Oxalis erythrorhiza Gillies ex Hooker et Arnott (Oxalidaceae), was reported against Trypanosoma cruzi and Leishmania spp. Additionally, antiprotozoan activity against Plasmodium falciparum was reported for its methylated derivative (ME). PURPOSE: To evaluate the potential anti-Trypanosoma cruzi activity of EMB, ME and 2,5-di-O-methylembelin (DME) and analyze the possible mechanism of action. STUDY DESIGN/METHODS: EMB was isolated by a chromatographic method from the air-dried ground whole plant. To evaluate the effects of methylation, ME and DME were synthesized and tested against T. cruzi epimastigotes and trypomastigotes. The most active compound ME was evaluated against amastigotes. Ultrastructural alterations, ROS generation and the effect on mitochondrial activity of ME were measured. RESULTS: Compounds inhibited the proliferation of epimastigotes. ME was also active against intracellular amastigotes. Mitochondrial alterations were observed by TEM. Additionally, ME modified the mitochondrial activity, and induced an increase in ROS levels. These evidences postulate the mitochondrion as a possible target of ME. CONCLUSION: ME inhibited amastigotes proliferation, thus being a potential lead compound for the treatment of Chagas' disease.
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Benzoquinonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/ultraestrutura , Animais , Doença de Chagas/tratamento farmacológico , Chlorocebus aethiops , Mitocôndrias/ultraestrutura , Plantas , Espécies Reativas de Oxigênio/metabolismo , Células VeroRESUMO
Annona emarginata (Schltdl.) H. Rainer, commonly known as "arachichú", "araticú", "aratigú", and "yerba mora", is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (-) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250â»1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16â»125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250â»500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound-(R)-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl (E)-3-(4-hydroxyphenyl)acrylate (1). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12â»6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.
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Annona/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Argentina , Flores/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Medicina Tradicional , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Casca de Planta/química , Folhas de Planta/químicaRESUMO
The seriated extracts of petroleum ether (PE-E), dichloromethane (DCM-E) and methanol extracts (MeOH-E) from the aerial parts of the native South American plant Tetraglochin ameghinoi (Rosaceae), were evaluated regarding their antioxidant and antibacterial activities. The antioxidant properties were evaluated by free radical scavenging methods (DPPH and TEAC), ferric-reducing antioxidant power (FRAP) and lipoperoxidation in erythrocytes (LP), while the antibacterial activity was performed against Gram-positive and Gram-negative bacteria according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The chemical and biological analyses of this plant are very important since this bush is currently used in traditional medicine as a cholagogue and digestive. The polar MeOH-E showed the highest antioxidant activities (17.70 µg/mL in the DPPH assay, 381.43 ± 22.38 mM TE/g extract in the FRAP assay, 387.76 ± 91.93 mg TE/g extract in the TEAC assay and 93.23 + 6.77% in the LP assay) and it was selected for chromatographic isolation of its components. These components were found to be four acetophenones, including the new phloracetophenone glucoside: 4',6',-dihydroxy-2'-O-(6â³-acetyl)-ß-d-glucopyranosylacetophenone or IUPAC name: (6-(2-acetyl-3,5-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl acetate, whose structure was elucidated by NMR and MS methods. In addition, twenty-six compounds, including five of these acetophenone derivatives, two sugars, six flavonoids, eleven phenolic acids and two triterpenes, were identified based on UHPLC-OT-MS and PDA analysis on the MeOH-E. The results support the medicinal use of the plant.
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Antioxidantes/metabolismo , Metaboloma/fisiologia , Metabolômica , Rosaceae/metabolismo , Antioxidantes/química , Rosaceae/químicaRESUMO
BACKGROUND: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD). PURPOSE: To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts. STUDY DESIGN AND METHODS: AChE and BChE inhibitory activities were evaluated with the Ellman's spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out. RESULTS: Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC50â¯=â¯1.84 - 15.40⯵g/ml) and moderate BChE (IC50â¯=â¯23.74 - 136.40⯵g/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular behavior in the active site among alkaloids possessing different in vitro inhibitory activities. CONCLUSION: Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp.
Assuntos
Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/farmacologia , Amaryllidaceae/química , Inibidores da Colinesterase/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Argentina , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos/métodos , Cromatografia Gasosa-Espectrometria de Massas , Modelos Moleculares , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/químicaRESUMO
A series of benzyl-substituted thiobenzoazoles were synthesized by an environmentally friendly approach, to search for new antifungal agrochemicals. Compounds were prepared starting from 2-mercaptobenzoazoles, using KOH, benzyl halides, and water, resulting in a simple and ecological method. New antifungals were tested against a group of phytopathogenic fungi. Two compounds showed an interesting activity against Botrytis cinerea, Fusarium oxysporum, and Aspergillus spp.: 2-((4-(trifluoromethyl)benzyl)thio)benzo[d]thiazole, 3ac, and 2-((4-methylbenzyl)thio)benzo[d]thiazole, 3al. Thus, 3ac and 3al can be considered as broad spectrum antifungal agents. Furthermore, two new compounds, 2-((4-iodobenzyl)thio)benzo[d]thiazole, 3aj, and 2-(benzylthio)benzo[d]oxazole, 3ba, showed better inhibitory effect against Botrytis cinerea and Fusarium oxysporum when compared to the commercial fungicide Captan. Thus, 3aj and 3ba can be considered reduced-spectrum antifungals.
Assuntos
Fungicidas Industriais/síntese química , Fungicidas Industriais/farmacologia , Aspergillus/efeitos dos fármacos , Azóis/química , Compostos de Benzil/química , Botrytis/efeitos dos fármacos , Fungicidas Industriais/química , Fusarium/efeitos dos fármacos , Química Verde , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
The emergence of old and new antibiotic resistance created in the last decades revealed a substantial medical need for new classes of antimicrobial agents. The antimicrobial activity of sulfa drugs is often enhanced by complexation with metal ions, which is in concordance with the well-known importance of metal ions in biological systems. Besides, sulfonamides and its derivatives constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid, antiviral and anticancer activities, among others. The purpose of this work has been the obtainment, characterization and determination of biological properties (antibacterial, antifungal, mutagenicity and phytotoxicity) of a new Co(III)-sulfathiazole complex: Costz, besides of its interaction with bovine serum albumin (BSA). The reaction between sodium sulfathiazole (Nastz) and cobalt(II) chloride in the presence of H2O2 leads to a brown solid, [CoIII(stz)2OH(H2O)3], (Costz). The structure of this compound has been examined by means of elemental analyses, FT-IR, 1H NMR, UV-Visible spectrometric methods and thermal studies. The Co(III) ion, which exhibits a distorted octahedral environment, could coordinate with the N thiazolic atom of sulfathiazolate. The complex quenched partially the native fluorescence of bovine serum albumin (BSA), suggesting a specific interaction with the protein. The Costz complex showed, in vitro, a moderate antifungal activity against Aspergillus fumigatus and A. flavus. As antibacterial, Costz displayed, in vitro, enhanced activity respective to the ligand against Pseudomonas aeruginosa. Costz did not show mutagenic properties with the Ames test. In the Allium cepa test the complex showed cytotoxic properties but not genotoxic ones. These results may be auspicious, however, further biological studies are needed to consider the complex Costz as a possible drug in the future.