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BACKGROUND: Extrusion cooking of cereal-legume flour mixture is an innovative strategy to introduce nutrient-enriched ready-to-eat snacks to the market. However, this thermal process triggers the formation of compounds that could impact safety aspects of these products. Maillard reaction markers and the end products known as melanoidins were evaluated to assess the toxicological and bioactive profiles of extruded snacks from corn-plus-common-bean-flour combinations. Different molecular weight fractions were isolated and purified to analyze their antioxidant activity and to investigate the role of melanoidins. RESULTS: The snack formulated with an 84:16 ratio of corn:common bean flours exhibited an enhanced toxicological profile. It displayed the lowest levels of acrylamide and furanic compounds, along with reduced blockage of lysine residues in the protein. Extrusion increased the antioxidant activity of uncooked flours (30 to 64%) and total phenolic compounds (26 to 50%), and decreased the available lysine (-72.7 to -79.5%). During the fractionation process, it was established that compounds within the range of 3-10 kDa made the greatest contribution to antioxidant activity. The fraction greater than 10 kDa, which included melanoidins, displayed 7 to 33% lower antioxidant activity. The purification of the fraction greater than 10 kDa revealed that pure melanoidins represented approximately one-third of the antioxidant activity in that fraction. Non-covalent adducts linked to the melanoidin core therefore had a relevant role in the antioxidant action of formulated snacks. CONCLUSION: This investigation illustrates the importance of considering both potential risks and associated benefits of compounds formed during the Maillard reaction while developing new extruded snacks. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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The increasing prevalence and complications related to liver diseases (caused by infection, toxic agents, or metabolic syndrome), together with insufficient existence of treatments, make evident the need for better therapeutic alternatives. Therefore, the aim of this study was to determine the effect of 4-hydroxychalcone (4-HC) as preventive and curative treatment in acute and chronic liver injury, respectively. Liver damage was induced with carbon tetrachloride (CCl4) in Wistar rats. Rats were divided into two groups: (1) acute liver injury and (2) chronic liver injury. In turn, each group was divided into four subgroups: (i) control (water); (ii) dimethyl sulfoxide 10%; (iii) CCl4; and (iv) 4-HC. The pre-treatment with 4-HC decreased transaminases, IL-6 serum levels, and hepatic malondialdehyde, increased IL-10 serum levels and hepatic glutathione, and decreased liver damage (necrosis, steatosis, and inflammatory infiltrate). In contrast, treatment with 4-HC after the induction of chronic liver injury decreased IL-6 serum levels and liver damage (steatosis, inflammatory infiltrate, ballooning cells, steatofibrosis, and fibrosis degree). Thus, the 4-HC treatment is proposed as a preventive treatment against acute liver injury; moreover, these results suggested the potential of 4-HC as a curative treatment against chronic liver injury, but other scheme treatments must be evaluated in future.
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Chalconas , Doença Hepática Induzida por Substâncias e Drogas , Fígado Gorduroso , Hepatopatias , Animais , Tetracloreto de Carbono/toxicidade , Chalconas/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Fígado Gorduroso/metabolismo , Glutationa/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Fígado , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Transaminases/metabolismoRESUMO
Imine functionality is found in many compounds with important biological activity. Thus, the development of novel synthetic approaches for imines is important. In this work, it is propose an easy, eco-friendly and straightforward synthesis pathway of aryl imines under microwave irradiation catalyzed by Alumina-sulfuric acid. In addition, the in vitro enzymatic inhibition, antioxidant activity and molecular docking studies were performed. The aryl imines were isolated with yields in the range of 37-94%. All aryl imines synthesized were evaluated for in vitro inhibitory potential against α-glucosidase and α-amylase enzymes and the results exhibited that the most of the compounds displayed inhibitory activity against both enzymes. The (E)-1-(4-nitrophenyl)-N-(pyridin-2-yl)methanimine (3d) was 1.15-fold more active than acarbose against α-amylase whilst the (E)-1-phenyl-N-(pyridin-2-yl)methanimine (3c) displayed similar activity that acarbose against α-glucosidase. The molecular docking studies in α-glucosidase and α-amylase reveal that aryl imines mainly establish an H-bond with the R2-subtituent and hydrophobic interactions with the R1-subtituent. The docking analysis reveals these synthetic aryl imines 3d-i interact in same active site than acarbose drug in both enzymes.
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Inibidores de Glicosídeo Hidrolases/farmacologia , Iminas/farmacologia , Simulação de Acoplamento Molecular , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Animais , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Iminas/síntese química , Iminas/química , Estrutura Molecular , Relação Estrutura-Atividade , Suínos , alfa-Amilases/metabolismoRESUMO
Worldwide studies towards development of new drugs with a lower rate in emergence of bacterial resistance have been conducted. The molecular docking analysis gives a possibility to predict the activity of new compounds before to perform their synthesis. In this work, the molecular docking analysis of 64 Linezolid dipeptide-type analogues was performed to predict their activity. The most negative scores correspond to six Fmoc-protected analogues (9as, 9bs, 9bu, 10as, 10ax and 10ay) where Fmoc group interacts in PTC for Linezolid. Twenty-six different Fmoc-protected Linezolid dipeptide-type analogues 9(as-bz) and 10(as-bz) were synthesized and tested in antimicrobial experiments. Compounds 9as, 9ay, 9ax, 10as, 10ay and 9bu show significant activity against group A Streptococcus clinical isolated. Analogue 10ay also display high activity against ATCC 25923 Staphylococcus aureus strain and MRSA-3, MRSA-4 and MRSA-5 clinical isolates, with MIC values lower than Linezolid. The highest activity against multidrug-resistant clinical isolates of Mycobacterium tuberculosis was exhibited by 9bu. Finally, a cytotoxicity assay with ARPE-19 human cells revealed a non-cytotoxic effect of 9bu and 10ay at 50 and 25 µM, respectively.
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Antibacterianos/farmacologia , Dipeptídeos/farmacologia , Desenho de Fármacos , Linezolida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dipeptídeos/síntese química , Dipeptídeos/química , Relação Dose-Resposta a Droga , Humanos , Linezolida/síntese química , Linezolida/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of l-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) to obtain N,N-dibenzylamino Linezolid analogues 4 and 5. A hydrogenolysis reaction over 4 and 5 resulted in amino-free Linezolid analogues 6 and 7, which were acetylated to reach diasteromeric Linezolid analogues 8 and 9. The six Linezolid analogues 4-9 show in vitro antiparasitic activity against Hymenolepis nana cestode, but not against several bacterial strains. Interestingly, compounds 6, 7 and 9 exhibit high potency, having shorter paralysis and death times after exposure (6-10 and 18-21 min, respectively), shorter than those found with antihelmintic compound Praziquantel (20 and 30 min) at 20 mg/mL. In addition, a cytocompatibility assay of 6-9 with human cells (ARPE-19 cells) demonstrate a non-cytotoxic effect at 0.4 mM. These results show the pharmacological potential of the newly reported Linezolid-type analogues as antiparasitic agents against Hymenolepis nana.
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Antibacterianos/farmacologia , Antiparasitários/farmacologia , Hymenolepis nana/efeitos dos fármacos , Linezolida/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antiparasitários/síntese química , Antiparasitários/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Linezolida/síntese química , Linezolida/química , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-AtividadeRESUMO
The high intake of sweetened drinks is associated with obesity and insulin resistance. These pathologies are directly related to the development of nonalcoholic fatty liver disease (NAFLD), considered a condition of metabolic syndrome (MS). Due to their increasing worldwide prevalence, experimental animal models have been developed to gain a better understanding of its physiopathology; notwithstanding, few studies have evaluated its progression in association with MS and ingestion of sweetened drinks. Therefore, the aim of this study was to understand the pathophysiologic characteristics of NAFLD related to sucrose concentration and time of ingestion in rats. Wistar rats were divided into 2 groups with free access to either tap water or 30% sucrose, and euthanized at 12, 16, or 20 weeks; and 2 additional groups were given free access to either 40% or 50% sucrose and were euthanized at 20 weeks. Biochemical parameters and levels of serum cytokines were measured, and histology was performed. Ingestion of 30% sucrose induced liver steatosis until 16 weeks (grade 2) and 20 weeks (grade 3). Meanwhile, during 20 weeks, 40% sucrose induced grade 5 of nonalcoholic steatohepatitis (NASH) and 50% sucrose induced grade 6 of NASH and fibrosis. This study demonstrated that increasing time of induction and concentration of sucrose ingestion resulted in a higher grade of NAFLD.
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Sacarose Alimentar/administração & dosagem , Sacarose Alimentar/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Peso Corporal/fisiologia , Citocinas/sangue , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade/sangue , Obesidade/etiologia , Obesidade/patologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Red arils of Pithecellobium dulce fruit, commonly known as guamuchil, show high antioxidant (AOx) and α-glucosidase inhibitory (IαG) activities, which have been mainly associated with the content of unknown anthocyanins. In this study, the AOx (i.e., DPPH and ABTS as Trolox equivalents, µmol TE/g) and IαG (as half-maximal inhibitory concentration, IC50, mg/mL) activities of the anthocyanin-rich fraction (ARF) obtained from red arils were contrasted with those of the methanol extract (ME), and the main ARF anthocyanins were characterized by HPLC-DAD-ESI-MS, GC-MS and 1H-NMR. The AOx and IαG values of the ARF (DPPH = 597.8; ABTS = 884.01; IαG = 0.06) were better than those of the ME (DPPH = 41.5; ABTS = 142.3; IαG = 17.5); remarkably, the ARF IαG value was about 42 times lower than that of acarbose. The main anthocyanins in ARF were pelargonidin 3-O-glucoside and cyanidin 3-O-glucoside. Thus, the consumption of red P. dulce arils could provide health benefits for prevention/treatment of chronic degenerative diseases such as diabetes.
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Antocianinas/análise , Antocianinas/farmacologia , Antioxidantes/farmacologia , Fabaceae/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Antocianinas/química , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Glucosídeos/análise , Glucosídeos/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
CONTEXT: Helicteres vegae Cristóbal (Sterculiaceae) (Hv) and Heliopsis sinaloensis B.L. Turner (Asteraceae) (Hs) are endangered and poorly studied plant species; related plants have been used against chronic-degenerative and infectious diseases. Therefore, Hv and Hs could be sources of bioactive compounds against these illnesses. OBJECTIVE: To determine the chemical composition and biological activities (antioxidant, antimutagenic and antimicrobial) of Hv and Hs leaves (L) and stems (S). MATERIALS AND METHODS: Methanol extracts (ME) of each plant/tissue were evaluated for their phytochemicals; phenolics (HPLC-DAD-ESI-MS); antioxidant activity (AA) (0.125-4 mg/mL) (DPPH, ABTS, ORAC and ß-carotene discoloration); antimutagenicity (0.5 and 1 mg/plate) (Ames assay, tester strain Salmonella enterica serovar Typhimurium YG1024, 1-nitropyrene as mutagen); activity against human pathogens (1 mg/mL); and toxicity (0.01-2 mg/mL) (Artemia salina assay). RESULTS: All ME showed flavonoids and triterpenes/steroids. The ME-SHv had the highest content of total phenolics (TP) (2245.82 ± 21.45 mg GAE/100 g d.w.) and condensed tannins (603.71 ± 1.115 mg CE/100 g d.w.). The compounds identified were flavonoids (kaempferol 7-O-coumaroylhexoside, and two kaempferol 7-O-rhamnosylhexosides) and phenolics [rosmarinic acid, and 3'-O-(8â³-Z-caffeoyl) rosmarinic acid]. The ME-LHs showed the highest content of flavonoids (357.88 mg RE/g d.w.) and phenolic acids (238.58 mg CAE/g d.w.) by HPLC. The ME-SHv showed the highest AA. All ME were strong antimutagens (63.3-85.7%). Only the Hs extracts were toxic (ME-LHs, LC50 = 94.9 ± 1.7 µg/mL; ME-SHs, LC50 = 89.03 ± 4.42 µg/mL). DISCUSSION AND CONCLUSIONS: Both Hv and Hs are potential sources of preventive and therapeutic agents against chronic-degenerative diseases.
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Anti-Infecciosos/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Asteraceae/química , Malvaceae/química , Extratos Vegetais/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/toxicidade , Antimutagênicos/química , Antimutagênicos/isolamento & purificação , Antimutagênicos/toxicidade , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Artemia/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Benzotiazóis/química , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão , Giardia lamblia/efeitos dos fármacos , Giardia lamblia/crescimento & desenvolvimento , Metanol/química , Testes de Sensibilidade Microbiana , Testes de Mutagenicidade , Capacidade de Absorbância de Radicais de Oxigênio , Testes de Sensibilidade Parasitária , Fitoterapia , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Caules de Planta/química , Plantas Medicinais , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Solventes/química , Espectrometria de Massas por Ionização por Electrospray , Ácidos Sulfônicos/química , beta Caroteno/químicaRESUMO
A regioselective synthesis has been developed for the preparation of a series of N,N'-disubstituted 4,4'-carbonylbis(carbamoylbenzoic) acids and N,N'-disubstituted bis(carbamoyl) terephthalic acids by treatment of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (1) and 1,2,4,5-benzenetetracarboxylic dianhydride (2) with arylalkyl primary amines (A-N). The carbamoylcarboxylic acid derivatives were synthesized with good yield and high purity. The specific reaction conditions were established to obtain carbamoyl and carboxylic acid functionalities over the thermodynamically most favored imide group. Products derived from both anhydrides 1 and 2 were isolated as pure regioisomeric compounds under innovative experimental conditions. The chemo- and regioselectivity of products derived from dianhydrides were determined by NMR spectroscopy and confirmed by density functional theory (DFT). All products were characterized by NMR, FTIR, and MS.
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Anidridos/química , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Técnicas de Química Sintética , Modelos Moleculares , Conformação MolecularRESUMO
Staphylococcus aureus is one of the most common causes of nosocomial infections. The purpose of this study was the synthesis and in vitro evaluation of antimicrobial activity of 10 new 3-oxazolidin-2-one analogues on 12 methicillin resistant S. aureus (MRSA) clinical isolates. S. aureus confirmation was achieved via catalase and coagulase test. Molecular characterization of MRSA was performed by amplification of the mecA gene. Antimicrobial susceptibility was evaluated via the Kirby-Bauer disc diffusion susceptibility test protocol, using commonly applied antibiotics and the oxazolidinone analogues. Only (R)-5-((S)-1-dibenzylaminoethyl)-1,3-oxazolidin-2-one (7a) exhibited antibacterial activity at 6.6 µg. These results, allow us to infer that molecules such as 7a can be potentially used to treat infections caused by MRSA strains.
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Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxazolidinonas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/síntese química , Artemia/efeitos dos fármacos , Proteínas de Bactérias/genética , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla , Oxazolidinonas/efeitos adversos , Oxazolidinonas/síntese química , Proteínas de Ligação às Penicilinas , Inibidores da Síntese de Proteínas/efeitos adversos , Inibidores da Síntese de Proteínas/síntese química , Inibidores da Síntese de Proteínas/farmacologia , Resistência beta-Lactâmica/genéticaRESUMO
This study reports the in silico design of 30 6H-1,2-oxazin-6-ones against DHFR and PTC antimicrobial targets. Docking compounds 1, 3, 4, 6, and 8 with both enzymes was favorable, outperforming Trimethoprim with DHFR. Therefore, 12 6H-1,2-oxazin-6-ones, including the most promising compounds, were synthesized through an aminolysis reaction of ß-cyanoketones with hydroxylamine hydrochloride, obtaining moderate to high yields (55-88%). Subsequently, antibacterial studies were conducted against five bacteria: four Gram-positive MRSA (ATCC 43300 and three clinical isolates) and one Gram-negative (E. coli ATCC 25922). Compounds 1, 2, 3, 4, 6, and 8 inhibited bacterial growth with MIC values ranging from 3.125 to 200 µg mL-1. Compound 1 showed better activity against Gram-positive bacteria than Linezolid. Toxicity assays indicated no adverse effects of the active oxazinones in silico and in vitro. This study demonstrated the antibacterial potential of the selected 6H-1,2-oxazin-6-ones against resistant human pathogenic bacteria.
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The inflammatory process, although beneficial, can produce tissue damage and systemic damage when uncontrolled. Effective therapeutic alternatives with little or no side effects are of great therapeutic interest. This study aimed to determine the phytochemical composition of bark extracts from J. cordata, an endemic plant from México, and evaluate their in vitro anti-inflammatory activity. Hexane, ethyl acetate, and methanol extracts were characterized by qualitative phytochemical tests, and their bioactive groups were identified by 1H NMR and gas chromatography coupled to mass spectrometry (GC-MS). The extract's anti-inflammatory activity was evaluated as nitric oxide (NO) production and their cytotoxicity by an MTS cell proliferation assay in lipopolysaccharide (LPS)-activated RAW 264.7 cells at concentrations of 1-100 µg/mL. The hexane extract contained fatty acids, fatty esters, phytosterols, alkanes, vitamin E, and terpenoids; the ethyl acetate extract showed fatty acids, fatty esters, aromatic aldehyde, phytosterols, vitamin E, and terpenoids, while the methanolic extract showed fatty esters, fatty acid, aromatics aldehydes, and alcohol. The ethyl acetate extract showed the highest inhibition of NO production, followed by the methanolic extract and the hexane extract, without affecting the viability of RAW 264.7 macrophage cells. The results suggest that J. cordata extracts are a potential source of bioactive compounds with anti-inflammatory potential.
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Benzimidazolones have shown biological activities, including antihyperglycemic and hypoglycemic, by inhibiting or activating of α-glu and GK. The aim of this study is the rational design of compounds using in silico assays to delimitate the selection of structures to synthesize and the in vitro evaluation of benzimidazolone derivatives in blood glucose control. A docking of 23 benzimidazolone derivatives was performed; selecting the compounds with better in silico profiles to synthesize by microwave-irradiation/conventional heat and evaluate in enzymatic in vitro evaluation. Compounds 2k, 2m, 2r, and 2s presented the best in silico profiles, showing good affinity energy (-10.9 to -8.6 kcal mol-1) and binding with catalytic-amino acids. They were synthesized at 70 °C and 24 h using DMF as the solvent and potassium carbonate (yield: 22-38%). The results with α-glu showed moderate inhibition of 2k (14 ± 1.23-29 ± 0.45), 2m (12 ± 2.21-36 ± 0.30), 2r (7 ± 2.21-13 ± 1.34), and 2s (11 ± 0.74-35 ± 2.95) at evaluated concentrations (0.1 to 100 µg mL-1). The GK activation assay showed an enzymatic activity increase; compound 2k increased 1.31 and 2.83 more than normal activity, 2m (2.13-fold), 2s (2.86 and 3.74-fold) at 100 and 200 µg mL-1 respectively. The present study showed that the 2s derivative presents moderate potential as an α-glu inhibitor and a good activator potential of GK, suggesting that this compound is a good candidate for blood glucose control through antihyperglycemic and hypoglycemic mechanisms.
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Medicines for chronic inflammation can cause gastric ulcers and hepatic and renal issues. An alternative treatment for chronic inflammation is that of natural bioactive compounds, which present low side effects. Extracts of Jatropha cordata (Ortega) Müll. Arg. have been evaluated for their cytotoxicity and anti-inflammatory activity; however, testing pure compounds would be of greater interest. Campesteryl palmitate, n-heptyl ferulate, palmitic acid, and a mixture of sterols, i.e., brassicasterol, campesterol, ß-sitosterol, and stigmasterol, were obtained from an ethyl acetate extract from J. cordata (Ortega) Müll. Arg. bark using column chromatography. The toxicity and in vitro anti-inflammatory activities were evaluated using RAW 264.7 murine macrophage cells. None of the products assessed exhibited toxicity. The sterol mixture exhibited greater anti-inflammatory activity than the positive control, and nitric oxide (NO) inhibition percentages were 37.97% and 41.68% at 22.5 µg/mL and 30 µg/mL, respectively. In addition, n-heptyl ferulate decreased NO by 30.61% at 30 µg/mL, while campesteryl palmitate did not show anti-inflammatory activity greater than the positive control. The mixture and n-heptyl ferulate showed NO inhibition; hence, we may conclude that these compounds have anti-inflammatory potential. Additionally, further research and clinical trials are needed to fully explore the therapeutic potential of these bioactive compounds and their efficacy in treating chronic inflammation.
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Pithecellobium dulce is distributed in America and Asia where is widely used in traditional medicine. This study describes the bioguided fractionation of the methanol extract (ME) obtained from the P. dulce fruit that showed in vitro activity against Hymenolepis nana; Artemia salina assay was used to determine toxicity; and the purified compound was computationally analysed to obtain its absorption-distribution-metabolism-excretion-and-toxicity properties (ADMET). The ME and its fractions were more active than praziquantel (PZQ), and the purified compound was characterized as N-malonyl-(+)-tryptophan (NMT). Parasites treated with NMT showed shorter paralysis and death times (5 and 7 min) than those treated with PZQ (15 and 30 min), both used at 20 mg/mL. Toxicity and ADMET prediction results supported the slight-hazardousness and efficacy of the assayed fractions/compound. This is the first report of the antiparasitary activity of both the P. dulce ME and NMT, showing their potential to treat human H. nana infections.
Assuntos
Fabaceae/química , Frutas/química , Hymenolepis nana/fisiologia , Triptofano/isolamento & purificação , Triptofano/farmacologia , Animais , Artemia/efeitos dos fármacos , Fracionamento Químico , Humanos , Hymenolepis nana/efeitos dos fármacos , Extratos Vegetais/farmacologiaRESUMO
Nowadays, infectious diseases caused by drug-resistant bacteria have become especially important. Linezolid is an antibacterial drug active against clinically important Gram positive strains; however, resistance showed by these bacteria has been reported. Nanotechnology has improved a broad area of science, such as medicine, developing new drug delivery and transport systems. In this work, several covalently bounded conjugated nanomaterials were synthesized from multiwalled carbon nanotubes (MWCNTs), a different length oligoethylene chain (S n ), and two linezolid precursors (4 and 7), and they were evaluated in antibacterial assays. Interestingly, due to the intrinsic antibacterial activity of the amino-oligoethylene linezolid analogues, these conjugated nanomaterials showed significant antibacterial activity against various tested bacterial strains in a radial diffusion assay and microdilution method, including Gram negative strains as Escherichia coli (11 mm, 6.25 µg mL-1) and Salmonella typhi (14 mm, ≤0.78 µg mL-1), which are not inhibited by linezolid. The results show a significant effect of the oligoethylene chain length over the antibacterial activity. Molecular docking of amino-oligoethylene linezolid analogs shows a more favorable interaction of the S 2-7 analog in the PTC of E. coli.
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A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC(50) values were 12.72, 15.05 and 15.31 microg/mL, respectively; these are potential leads for the development of antigiardial compounds.
Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Chalconas/síntese química , Chalconas/farmacologia , Giardia lamblia/efeitos dos fármacos , Animais , Antiprotozoários/química , Chalconas/química , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
The water-soluble melanins (SM) of Randia echinocarpa fruit possess interesting biological activities and have been scarcely characterized. In this study, SM were obtained at boiling (SMBT) and room (SMRT) temperatures and characterized by UV-Vis, IR, thermogravimetric analysis, and GC-MS of the hydrolysis products of the SM; besides, the solid-state 13 C NMR, elemental analysis, and acute and sub-acute toxicity of the SMBT were determined. SMBT and SMRT contain organic acids and carbohydrates and their spectroscopic signals and thermograms were similar, but the SMBT yield was higher. The SMBT were characterized by their elemental composition (C 48.260 ± 0.011%, N 3.693 ± 0.009% and H 6.093 ± 0.076%) consistent with the presence of aromatic rings and eumelanins, degradation temperature at 300°C, 13 C NMR signals supporting melanin-bonding with carbohydrates and organic acids, and innocuity in Balb/C mice (acute assay, LD50 > 5 g/kg b.w.; sub-acute assay, no lethality at 500 mg/kg b.w. for 30 days). PRACTICAL APPLICATIONS: The consumption of melanins has been associated with health benefits because of their biological activities (e.g., antioxidant, immunostimulatory, UV- and radiation-protective). Randia echinocarpa is employed in Mexican traditional medicine against chronic degenerative diseases (e.g., cancer and diabetes) and ailments of organs (e.g., kidney and lung) and systems (e.g., circulatory and gastrointestinal). The R. echinocarpa fruit contains water-soluble melanins (SM) that inhibit carbohydrate-digestive enzymes and show high antioxidant activity; thus, SM could be useful for the prevention and treatment of diabetes. This study showed that the SM structure contains melanin-bonding organic acids and carbohydrates, which could be associated with the SM solubility and higher yield, and that SMBT were innocuous in the acute and sub-acute assays in mice. Thus, the R. echinocarpa SMBT could be used as safe potential ingredients to develop functional products.
Assuntos
Frutas/química , Melaninas/análise , Extratos Vegetais/análise , Animais , Camundongos , Camundongos Endogâmicos BALB C , Rubiaceae , Solubilidade , Testes de ToxicidadeRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Despite the impact of this pathology in the population, nowadays there is no specific treatment for this disease, focusing its treatment on risks factors. However, it is imperative the existence of a specific treatment, due to this, the aim of this study was to determine the therapeutic effect of treatment with metformin, 4-hydroxychalcone or co-treatment on male Wistar rats with NAFLD. Wistar rats were divided into two groups with free access to either tap water or 50% sucrose (NAFLD) during 25 weeks. After 20 weeks of induction each were divided into four groups that received daily p.o. administration of: i) saline solution (1â¯ml); ii) metformin (200â¯mg/kg/day); iii) 4-hydroxychalcone (80â¯mg/kg/day) and i.v.) co-treatment (metformin plus 4-hydroxychalcone at the doses mentioned above), for 5 weeks. In healthy rats: metformin and co-treatment modified food and total caloric intake and induced diarrhea; but none of the treatments changed the other parameters evaluated. Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-ß, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-α and TGF-ß, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-α, TGF-ß, liver steatosis and fibrosis. Our results showed that 4-hydroxychalcone treatment was the most effective among the treatments tested against NAFLD.
Assuntos
Chalconas/farmacologia , Metformina/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Chalconas/uso terapêutico , Colágeno/biossíntese , Citocinas/sangue , Diarreia/complicações , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Nutrientes/metabolismo , Ratos , Ratos WistarRESUMO
The hymenolepiosis by Hymenolepis nana is a major public health problem in developing countries, and the commercial drugs against this parasitosis are not enough effective. The combination of antiparasitic and antioxidant agents has improved the treatment of some parasitoses. Thus, the development of new cestocidal and antioxidant agents to treat the hymenolepiosis cases is important. In the present study, four hydroxy- and four dihydroxy-chalcones were synthesized using the catalyst boron trifluoride diethyl etherate (BF3â¢OEt2). The antioxidant activity and antiparasitic against H. nana of chalcones were tested, as well as the toxicity by the brine shrimp lethality bioassay and the method of Lorke. The antioxidant activity was measured by three radical scavenging assays: 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP). The hydroxyl substitution pattern (number and position), mainly in ring B, was responsible for the chalcone antiparasitic activity. At least one meta or para hydroxyl group in ring B was essential for activity of the synthetic chalcones against H. nana; The time taken for the parasite to die by the 3b and 3e chalcones (20 mg/mL) treatment was up to six times lower than the control drug Praziquantel. On the other hand, chalcones with catechol structure in ring B (3g and 3h) showed the highest antioxidant values. The toxicity evaluations suggests that synthetic hydroxychalcones with cestocidal (3b and 3e) and antioxidant (3g and 3h) activities are safe compounds and potential in vivo agents to treat this parasitosis