Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.874
Filtrar
1.
Acta Crystallogr C Struct Chem ; 76(Pt 9): 914-920, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887863

RESUMO

The terpenoid (-)-Istanbulin A is a natural product isolated from Senecio filaginoides DC, one of the 270 species of Senecio (Asteraceae) which occurs in Argentina. The structure and absolute configuration of this compound [9a-hydroxy-3,4a,5-trimethyl-4a,6,7,8a,9,9a-hexahydro-4H,5H-naphtho[2,3-b]-furan-2,8-dione or (4S,5R,8R,10S)-1-oxo-8ß-hydroxy-10ßH-eremophil-7(11)-en-12,8ß-olide, C15H20O4] were determined by single-crystal X-ray diffraction studies. It proved to be a sesquiterpene lactone showing an eremophilanolide skeleton whose chirality is described as 4S,5R,8R,10S. Structural results were also in agreement with the one- and two-dimensional (1D and 2D) NMR and HR-ESI-MS data, and other complementary spectroscopic information. In addition, (-)-Istanbulin A is a polymorph of the previously reported form of (-)-Istanbulin A, form I; thus, the title compound is denoted form II or polymorph II. Structural data and a literature search allowed the chirality of Istanbulin A to be revisited. The antimicrobial and antifungal activities of (-)-Istanbulin A, form II, were evaluated in order to establish a reference for future comparisons and applications related to specific crystal forms of Istanbulins.


Assuntos
Antifúngicos/química , Furanos/química , Sesquiterpenos/química , Cristalografia por Raios X , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Estereoisomerismo
2.
Food Chem ; 333: 127537, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32683265

RESUMO

Antifungal bioplastic films were developed based on poly(lactic acid) (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) blends as PLA60/PBAT40 (PLA/PBAT) and PBAT60/PLA40 (PBAT/PLA) with incorporated trans-cinnamaldehyde using cast-extrusion. Trans-cinnamaldehyde was more compatible in PLA which exhibited plasticization that increased molecular mobility, crystallinity, permeability but limited volatile release and reduced film strength. Interaction of trans-cinnamaldehyde modified CO functional groups of PLA and PBAT. Phase separation was higher in PBAT/PLA films due to less surface adhesion in PBAT networks. Higher release of trans-cinnamaldehyde enhanced bread crystallinity but gave lower rate of hardness increase due to plasticization of starch and protein and reduced lipid crystallinity. Increased bread hardness correlated with decreased water activity that was effectively prevented by higher release of trans-cinnamaldehyde. Films containing trans-cinnamaldehyde (2-10%) showed high antifungal efficacy against Penicillium sp. and Aspergillus niger but low effective against Rhizopus sp. Trans-cinnamaldehyde reduced bacterial and fungal growth in breads, extending shelf-life for 21 days.


Assuntos
Acroleína/análogos & derivados , Adipatos/química , Alcenos/química , Pão , Embalagem de Alimentos/métodos , Ácidos Ftálicos/química , Poliésteres/química , Acroleína/química , Antifúngicos/química , Pão/microbiologia , Permeabilidade , Amido/química
3.
SAR QSAR Environ Res ; 31(8): 571-583, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32628042

RESUMO

One of the most challenging issues when facing a Quantitative structure-activity relationship (QSAR) classification model is to deal with the descriptor selection. Penalized methods have been adapted and have gained popularity as a key for simultaneously performing descriptor selection and QSAR classification model estimation. However, penalized methods have drawbacks such as having biases and inconsistencies that make they lack the oracle properties. This paper proposes an adaptive penalized logistic regression (APLR) to overcome these drawbacks. This is done by employing a ratio (BWR) of the descriptors between-groups sum of squares (BSS) to the within-groups sum of squares (WSS) for each descriptor as a weight inside the L1-norm. The proposed method was applied to one dataset that consists of a diverse series of antimicrobial agents with their respective bioactivities against Candida albicans. By experimental study, it has been shown that the proposed method (APLR) was more efficient in the selection of descriptors and classification accuracy than the other competitive methods that could be used in developing QSAR classification models. Another dataset was also successfully experienced. Therefore, it can be concluded that the APLR method had significant impact on QSAR analysis and studies.


Assuntos
Antifúngicos/química , Candida albicans/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Modelos Logísticos , Modelos Moleculares
4.
J Environ Sci Health B ; 55(9): 835-843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32657210

RESUMO

Aflatoxins produced by Aspergillus parasiticus are toxic and carcinogenic metabolites. The biosynthesis of this mycotoxins is a complex process and involves at least 30 genes clustered within an approximately 82 kB gene cluster. In the present study, the effect of Capsicum chinense and Piper nigrum fruits on Aspergillus parasiticus growth and aflatoxin production were studied in relation to the expression of aflD, aflM, aflR, and aflS four; key genes of aflatoxins biosynthesis pathway. GC-EIMS analysis identified capsaicin (66,107 µg g-1) and piperine (1,138 µg g-1) as the most abundant compounds in C. chinense and P. nigrum fruits, respectively. The antifungal and anti-aflatoxigenic assays showed that C. chinense, P. nigrum, capsaicin, and piperine inhibited A. parasiticus growth and aflatoxins production in a dose-dependent manner. The piperine at 300 µg mL-1 produced higher radial growth inhibition (89%) and aflatoxin production inhibition (69%). The expression of aflatoxin biosynthetic genes was evaluated by quantitative real-time PCR (qRT-PCR) and revealed that aflatoxin inhibition occurring via downregulating the aflS and aflR, and subsequently aflD and aflM genes. These results will improve our understanding of the mechanism of aflatoxin regulation by C. chinense, P. nigrum, capsaicin, and piperine, and provides a reference for further study.


Assuntos
Aflatoxinas/metabolismo , Aspergillus/efeitos dos fármacos , Capsicum/química , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Piper nigrum/química , Aflatoxinas/genética , Alcaloides/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Aspergillus/genética , Aspergillus/crescimento & desenvolvimento , Aspergillus/metabolismo , Benzodioxóis/farmacologia , Vias Biossintéticas , Capsaicina/farmacocinética , Proteínas de Ligação a DNA/genética , Frutas/química , Proteínas Fúngicas/genética , Genes Fúngicos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Fatores de Transcrição/genética
5.
Int J Food Microbiol ; 330: 108766, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32659522

RESUMO

The aim of the study was to explore the antifungal and aflatoxin B1 inhibitory efficacy of nanoencapsulated antifungal formulation. Mixture design response surface methodology (RSM) was utilized to design the antifungal formulation (SBC 4:1:1) based on the combination of chemically characterized Ocimum sanctum (S), O. basilicum (B), and O. canum (C) against Aspergillus flavus. The SBC was incorporated inside the chitosan nanomatrix (Ne-SBC) using an ultrasonic probe (40 kHz) and interactions were confirmed by SEM, FTIR and XRD analysis. The results showed that the Ne-SBC possessed enhanced antifungal and aflatoxin B1 inhibitory effect over the free form of SBC. The biochemical and in silico results indicate that the antifungal and aflatoxin B1 inhibitory effect was related to perturbance in the plasma membrane function (ergosterol biosynthesis and membrane cation) mitochondrial membrane potential, C-sources utilization, antioxidant defense system, and the targeted gene products Erg 28, cytochrome c oxidase subunit Va, and Nor-1. In-situ observation revealed that Ne-SBC effectively protects the Avena sativa seeds from A. flavus and AFB1 contamination and preserves its sensory profile. The findings suggest that the fabrication of SBC inside the chitosan nano-matrix has promising use in the food industries as an antifungal agent.


Assuntos
Aflatoxina B1/antagonistas & inibidores , Antifúngicos/farmacologia , Microbiologia de Alimentos , Ocimum/química , Óleos Voláteis/farmacologia , Aflatoxina B1/metabolismo , Antifúngicos/química , Aspergillus flavus/efeitos dos fármacos , Aspergillus flavus/metabolismo , Quitosana/química , Quitosana/farmacologia , Composição de Medicamentos , Ocimum/classificação , Óleos Voláteis/química , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Sementes/microbiologia
6.
Chemosphere ; 258: 127352, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32554013

RESUMO

The production of metallic nanoparticles (NPs) by green and ecofriendly methods has received consideration during the recent past. The present study summarized the comparative production of titanium dioxide (TiO2) NPs by plant extracts of Trianthema portulacastrum (T2) and Chenopodium quinoa (T3) and by conventional chemical (sol-gel) method (T1). Synthesized TiO2-NPs were examined by high-tech. techniques such as X-Ray Diffraction (XRD), Fourier Transmission Infra-red (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray (EDX) spectroscope, SEM-EDS spot analysis and elemental mapping. Synthesized TiO2-NPs were applied on wheat rust (Ustilago tritici) for the evaluation of their antifungal activity against toxic plant pathogens. XRD results confirmed the (2θ) peak at 25.3 related to 101 anatase form. EDS-spot analysis and elemental mapping confirms the formation of TiO2-NPs by using these techniques. SEM secondary electrons (SEs) images demonstrated the nano range of particles in cluster form with fewer porous structures. The average size of all three TiO2-NPs was found less than 15 nm. FT-IR analysis of all three TiO2-NPs perfectly matched with the standard parameters. The NPs prepared by both sol-gel and green methods have a good antifungal response against U. tritici, and the green prepared TiO2-NPs were found to have the best antifungal activity against wheat rust especially NPs synthesized with the extract of C. quinoa. Overall, green method can be used for the large scale and less toxic synthesis of TiO2-NPs because of their wide range of environmental applications.


Assuntos
Antifúngicos/química , Nanopartículas/química , Titânio/química , Nanopartículas Metálicas/química , Microscopia Eletrônica de Varredura , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier , Triticum , Difração de Raios X
7.
Food Chem ; 330: 127211, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32540527

RESUMO

With the current agro-food industry demands for more environmentally-friendly production, the use of natural antifungal compounds extracted by emerging technologies led to a sustainable alternative to control microorganisms. Therefore, the present work aimed to: (i) determine antifungal activity against Colletotrichum gloeosporioides and Penicillium italicum of jackfruit leaf extracts obtained by different methods, and (ii) identify compounds by HPLC-DAD-ESI-MS. Microwave (MAE), high-hydrostatic pressure (HHP) and ultrasound (UAE) assisted extractions were tested, followed by fractionation with different polarity solvents. The concentration of total soluble phenols (TSP), tannins (TT) and flavonoids (TF) were determined. Differences not only in the amounts of extracted phytochemicals were found but in the antifungal properties (MAE against P. italicum and HHP against C. gloeosporioides at 5 mg/ml) as well as in the chemical composition determined by HPLC-MS. These results suggest the possible application of jackfruit leaf extracts as a suitable postharvest antifungal treatment.


Assuntos
Antifúngicos/química , Artocarpus/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Flavonoides/química , Penicillium/efeitos dos fármacos , Fenóis/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Taninos/química
8.
Food Chem ; 327: 127060, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32454280

RESUMO

OBJECTIVES: This study set out to highlight the in vitro and in vivo antifungal activity of an Ethanolic Extract of Red Brazilian Propolis (EERBP) and identify bioactive fractions effective against Colletotrichum musae. METHODS: Active fractions were detected by the thin-layer chromatography-bioautography method and characterised by HPLC-MSn. RESULTS: The in vitro results showed that EERBP had strong antifungal properties againstC. musae (81 ± 1% inhibition at 1.6 g GAE L-1). Medicarpin, (3S)-vestitol and (3S)-neovestitol were the main compounds identified in the EERBP extract (45% of all detected peaks). Two isolated fractions displayed inhibition percentages of 35 ± 4 and 42 ± 1%, respectively, on C. musae mycelial growth compared to the EERBP extract. The biological activity of the two fractions displayed an additive effect. CONCLUSION: A further in vivo investigation revealed that EERBP is a potential natural alternative for controlling banana crown rot.


Assuntos
Antifúngicos/química , Extratos Vegetais/química , Própole/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Brasil , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Delgada , Colletotrichum/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Própole/metabolismo , Espectrometria de Massas por Ionização por Electrospray
9.
AAPS PharmSciTech ; 21(5): 140, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419032

RESUMO

The present study is aimed at enhancing the skin penetration of ketoconazole by formulating it as transethosome. Ketoconazole-loaded transethosome formulations were prepared by conventional thin film evaporation and hydration method and were optimized using concentration of edge activator (span 80), ethanol and sonication time as factors and particle size, polydispersity index and entrapment efficiency as responses. The optimized formulation was further evaluated for in vitro diffusion, anti-fungal activity, ex vivo penetration and in vivo pharmacodynamic activity. The results of in vitro drug diffusion and ex vivo skin penetration studies demonstrated that the amount of drug diffused and penetrated through the skin was increased. Optimized transethosomes showed enhanced in vitro antifungal and in vivo pharmacodynamic activities against Candida albicans in Wistar albino rats when compared to conventional liposomes. Therefore, the developed ketoconazole encapsulated transethosome formulation is capable of enhancing the skin penetration of the drug by overcoming the stratum corneum barrier function and acting as an effective drug delivery system for ketoconazole through the skin for its anti-fungal activity.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/química , Administração Cutânea , Animais , Antifúngicos/farmacocinética , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Excipientes , Cetoconazol/administração & dosagem , Cetoconazol/química , Lipossomos , Tamanho da Partícula , Ratos , Ratos Wistar , Absorção Cutânea
10.
Mar Drugs ; 18(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344725

RESUMO

Sponge-associated fungi are attractive targets for the isolation of bioactive natural products with different pharmaceutical purposes. In this investigation, 20 fungi were isolated from 10 different sponge specimens. One isolate, the fungus Penicillium citrinum strain WK-P9, showed activity against Bacillus subtilis JH642 when cultivated in malt extract medium. One new and three known citrinin derivatives were isolated from the extract of this fungus. The structures were elucidated by 1D and 2D NMR spectroscopy, as well as LC-HRMS. Their antibacterial activity against a set of common human pathogenic bacteria and fungi was tested. Compound 2 showed moderate activity against Mycobacterium smegmatis ATCC607 with a minimum inhibitory concentration (MIC) of 32 µg/mL. Compound 4 exhibited moderate growth inhibition against Bacillus subtilis JH642, B. megaterium DSM32, and M. smegmatis ATCC607 with MICs of 16, 16, and 32 µg/mL, respectively. Furthermore, weak activities of 64 µg/mL against B. subtilis DSM10 and S. aureus ATCC25923 were observed for compound 4.


Assuntos
Antibacterianos/isolamento & purificação , Citrinina/isolamento & purificação , Penicillium/química , Poríferos/microbiologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Citrinina/química , Citrinina/farmacologia , Fungos/efeitos dos fármacos , Indonésia , Testes de Sensibilidade Microbiana , Penicillium/isolamento & purificação
11.
Food Chem ; 321: 126701, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32283502

RESUMO

The antifungal activity of a library of twenty-four aromatic methoximes was examined against five representative postharvest phytopathogenic fungi. The panel included Penicillium digitatum, Penicillium italicum, Rhizopus stolonifer, Botrytis cinerea and Monilinia fructicola, all of which cause relevant economic losses worldwide as a result of affecting harvested fruits. The minimum inhibitory concentrations and minimum fungicidal concentrations of each compound were defined and the main structure-activity relationships were determined. Although other congeners were more potent, drug likeliness considerations pointed to the methoxime derived from 2,4-dihydroxypropiophenone as the compound with the most suitable profile. The morphology of the colonies of the fungal strains treated with the methoxime was examined microscopically and the compound was also tested in freshly harvested peaches and oranges, exhibiting promising control profiles in both fruits, similar to those of the commercial agents Imazalil and Carbendazim.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Frutas/microbiologia , Oximas/química , Ascomicetos/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Citrus sinensis/efeitos dos fármacos , Citrus sinensis/microbiologia , Frutas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oximas/farmacologia , Penicillium/efeitos dos fármacos , Prunus persica/efeitos dos fármacos , Prunus persica/microbiologia , Rhizopus/efeitos dos fármacos , Relação Estrutura-Atividade
12.
Chem Biol Interact ; 320: 109028, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32119865

RESUMO

Reactive oxygen species (ROS) cause cell damage and death. To reverse these effects, cells produce substances such as reduced glutathione (GSH) that serve as substrates for antioxidant enzymes. One way to combat microbial resistance includes nullifying the effect of glutathione in microbial cells, causing them to die from oxidative stress. The compound 2-((5-nitrothiophen-2-yl)methylene)-N-(pyridin-3-yl) hydrazine carbothioamide (L10) is a new thiophene-thiosemicarbazone derivative with promising antifungal activity. The aim of this study was to evaluate its mechanism of action against Candida albicans using assays that evaluate its effects on redox balance. Treatment with L10 promoted significant changes in the minimum inhibitory concentration (MIC) values in ascorbic acid and GSH protection tests, the latter increasing up to 64-fold of the MIC. Using nuclear magnetic resonance, we demonstrated interaction of L10 and GSH. At concentrations of 4.0 and 8.0 µg/mL, significant changes were observed in ROS production and mitochondrial membrane potential. The cell death profile showed characteristics of initial apoptosis at inhibitory concentrations (4.0 µg/mL). Transmission electron microscopy data corroborated these results and indicated signs of apoptosis, damage to plasma and nuclear membranes, and to mitochondria. Taken together, these results suggest a possible mechanism of action for L10 antifungal activity, involving changes in cellular redox balance, ROS production, and apoptosis-compatible cellular changes.


Assuntos
Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Tiofenos/farmacologia , Tiossemicarbazonas/farmacologia , Antifúngicos/química , Humanos , Estrutura Molecular , Tiofenos/química , Tiossemicarbazonas/química
13.
Int J Food Microbiol ; 322: 108574, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32151821

RESUMO

Fungi are commonly identified as the cause for dairy food spoilage. This can lead to substantial economic losses for the dairy industry as well as consumer dissatisfaction. In this context, biopreservation of fermented dairy products using lactic acid bacteria, propionibacteria and fungi capable of producing a large range of antifungal metabolites is of major interest. In a previous study, extensive screening was performed in vitro and in situ to select 3 dairy fermentates (derived from Acidipropionibacterium jensenii CIRM-BIA1774, Lactobacillus rhamnosus CIRM-BIA1952 and Mucor lanceolatus UBOCC-A-109193, respectively) with antifungal activity. The aim of the present study was to determine the main compounds responsible for this antifungal activity. Fifty-six known antifungal compounds as well as volatiles were targeted using different analytical methods (conventional LC and GC, GC-MS, LC-QToF). The most abundant antifungal compounds in P. jensenii-, L. rhamnosus- and M. lanceolatus-derived fermentates corresponded to propionic and acetic acids, lactic and acetic acids, and butyric acid, respectively. Many other antifungal compounds (organic acids, free fatty acids, volatile compounds) were identified but at lower levels. In addition, an untargeted approach using nano LC-MS/MS identified a 9-amino acid peptide derived from αs2-casein in the L. rhamnosus-derived fermentate. This peptide inhibited M. racemosus and R. mucilaginosa in vitro. This study provides new insights on the molecules involved in antifungal activities of food-grade microorganism fermentates which could be used as antifungal ingredients in the dairy industry.


Assuntos
Antifúngicos/análise , Produtos Fermentados do Leite/análise , Conservantes de Alimentos/análise , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Reatores Biológicos , Produtos Fermentados do Leite/microbiologia , Fermentação , Microbiologia de Alimentos , Conservantes de Alimentos/química , Conservantes de Alimentos/metabolismo , Conservantes de Alimentos/farmacologia , Lactobacillus rhamnosus/isolamento & purificação , Lactobacillus rhamnosus/metabolismo , Mucor/isolamento & purificação , Mucor/metabolismo , Propionibacterium/isolamento & purificação , Propionibacterium/metabolismo , Rhodotorula/efeitos dos fármacos
14.
J Med Chem ; 63(7): 3522-3537, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32175733

RESUMO

Here, we present a rational approach that enhances the membrane selectivity of a prolific pore-forming peptide, melittin, based on experimental observations that the cationic polymer, ε-polylysine, disrupts bacterial membranes with greater affinity over mammalian cells when compared to poly-l-lysine and poly-d-lysine. We systematically replaced three α-lysine residues in melittin with ε-lysine residues and identified key residues that are important for cytotoxicity. We then assessed the antimicrobial properties of the modified peptides which carry two or three ε-lysyl residues. Two modified melittin peptides displayed rapid bactericidal properties against antibiotic-resistant strains, low innate resistance development by pathogenic bacteria, remained nonimmunogenic for T lymphocytes, and increased bioavailability in tear fluids. In proof-of-concept in vivo experiments, one of the peptides was noncytotoxic for ocular surfaces and had comparable antimicrobial efficacy to that of fluoroquinolone antibiotics. The results uncover a simple and potential strategy that can enhance the membrane selectivity of cytolytic peptides by ε-lysylation.


Assuntos
Antibacterianos/farmacologia , Membrana Celular/efeitos dos fármacos , Lisina/química , Meliteno/farmacologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Antibacterianos/química , Antibacterianos/uso terapêutico , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Bactérias/efeitos dos fármacos , Abelhas/química , Candida albicans/efeitos dos fármacos , Córnea/microbiologia , Córnea/patologia , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/patologia , Feminino , Humanos , Ceratite/tratamento farmacológico , Ceratite/patologia , Meliteno/química , Meliteno/uso terapêutico , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Estudo de Prova de Conceito , Coelhos , Lipossomas Unilamelares/metabolismo
15.
J Biosci Bioeng ; 130(1): 6-13, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32192842

RESUMO

Defensins are antibacterial peptides that function in the innate immune system. OsAFP1, a defensin identified from Oryza sativa (rice), exhibits antimicrobial activity against rice pathogens. Intriguingly, OsAFP1 was also shown to demonstrate potent antifungal activity against the human pathogenic fungus Candida albicans by inducing apoptosis in target cells, suggesting that OsAFP1 represents a potential new antibiotic candidate; however, further analyses, particularly at the structural level, are required to elucidate the mechanistic underpinnings of OsAFP1 antifungal activity. Here, we determined the three-dimensional structure of OsAFP1 using X-ray crystallography. OsAFP1 features the cysteine-stabilized αß structure highly conserved in plant defensins and presents a dimeric structure that appears necessary for antifungal activity. Superimposition of the OsAFP1 structure with that of Nicotiana alata NaD1 complexed with phosphatidic acid indicated that the target molecule is likely trapped between the S2-S3 loops of each OsAFP1 dimer. In lipid-binding analyses performed using nitrocellulose membranes immobilized with various membrane lipid components, OsAFP1 was found to bind to phosphatidylinositols (PIPs) harboring phosphate groups, particularly PI(3)P. These results indicate that OsAFP1 exerts antifungal activity by binding to PI(3)P contained in the C. albicans cell membrane, thereby applying cellular stress and inducing apoptosis. Furthermore, the OsAFP1 structure and site-specific-mutation analyses revealed that Arg1, His2, Leu4, Arg9, and Phe10 play critical roles in OsAFP1 dimer formation. Thus, our study provides novel insights into the antifungal mechanism of OsAFP1.


Assuntos
Defensinas/química , Defensinas/metabolismo , Oryza/metabolismo , Fosfatidilinositóis/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Cristalização , Defensinas/genética , Defensinas/farmacologia , Oryza/química , Oryza/genética , Fosfatidilinositóis/química , Proteínas de Plantas/genética , Proteínas de Plantas/farmacologia
16.
Chemistry ; 26(19): 4256-4260, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031278

RESUMO

We report the first chemical synthesis of eurysterol A, a cytotoxic and antifungal marine steroidal sulfate with a unique C8-C19 oxy-bridged cholestane skeleton. After C19 hydroxylation of cholesteryl acetate, used as an inexpensive commercial starting material, the challenging oxidative functionalization of ring B was achieved by two different routes to set up a 5α-hydroxy-7-en-6-one moiety. As a key step, an intramolecular oxa-Michael addition was exploited to close the oxy-bridge (8ß,19-epoxy unit). DFT calculations show this reversible transformation being exergonic by about -30 kJ mol-1 . Along the optimized (scalable) synthetic sequence, the target natural product was obtained in only 11 steps in 5 % overall yield. In addition, an access to (isomeric) 7ß,19-epoxy steroids with a previously unknown pentacyclic ring system was discovered.


Assuntos
Antifúngicos/síntese química , Esteroides/química , Esteróis/síntese química , Antifúngicos/química , Hidroxilação , Isomerismo , Estrutura Molecular , Oxirredução , Esteróis/química
17.
PLoS One ; 15(2): e0229414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32107486

RESUMO

Onychomycosis, or fungal nail infection, is a common fungal infection largely caused by dermatophyte fungi, such as Trichophyton rubrum or Trichophyton mentagrophytes, which affects a significant number of people. Treatment is either through oral antifungal medicines, which are efficacious but have significant safety concerns, or with topical antifungal treatments that require long treatment regimens and have only limited efficacy. Thus, an efficacious topical therapy remains an unmet medical need. Among the barriers to topical delivery through the nail are the physico-chemical properties of the antifungal drugs. Here, we explore the ability of a range of antifungal compounds with different hydrophilicities to penetrate the nail. Human nail discs were clamped within static diffusion (Franz) cells and dosed with equimolar concentrations of antifungal drugs. Using LC-MS/MS we quantified the amount of drug that passed through the nail disc and that which remained associated with the nail. Our data identified increased drug flux through the nail for the more hydrophilic compounds (caffeine as a hydrophilic control and fluconazole, with LogP -0.07 and 0.5, respectively), while less hydrophilic efinaconazole, amorolfine and terbinafine (LogP 2.7, 5.6 and 5.9 respectively) had much lower flux through the nail. On the other hand, hydrophilicity alone did not account for the amount of drug associated with/bound to the nail itself. While there are other factors that are likely to combine to dictate nail penetration, this work supports earlier studies that implicate compound hydrophilicity as a critical factor for nail penetration.


Assuntos
Antifúngicos/farmacologia , Antifúngicos/farmacocinética , Micoses/tratamento farmacológico , Doenças da Unha/tratamento farmacológico , Unhas/efeitos dos fármacos , Administração Tópica , Antifúngicos/administração & dosagem , Antifúngicos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Micoses/metabolismo , Micoses/microbiologia , Doenças da Unha/metabolismo , Doenças da Unha/microbiologia , Unhas/metabolismo , Unhas/microbiologia , Permeabilidade , Distribuição Tecidual
18.
J Mycol Med ; 30(2): 100924, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32037102

RESUMO

Cryptococcus neoformans, an encapsulated fungal pathogen is evolving as a major threat to immune-compromised patients and rarely to healthy individuals also. The cell wall bound capsular polysaccharide, melanin pigment and biofilm formation are major virulence factors that are known to contribute to cryptococcal meningitis. In the present study, a furanone derivative, (E)-5-benzylidenedihydrofuran-2(3H)-one (compound-6) was evaluated against biofilm of seven different strains of C. neoformans in melanized and non-melanized condition. In addition, the efficacy of compound-6 in activation of TLR-2, opsonophagocytosis, and modulation of cytokine expression during phagocytosis were studied. During the biofilm study, we found that moderate capsule size favored biofilm formation. Interestingly, the minimum biofilm eradication concentration (MBEC0.5) of melanized biofilm was found to be achieved at 1- to 1.7-fold higher MBEC0.5 of non-melanized cells. The maximum eradication of 77% and 69% of non-melanized and melanized biofilm were observed. The capsule size was reduced to half of its size with marked changes in morphology. Furthermore, expression of TLR2, iNOS and pro-inflammatory cytokines such as TNF-α, IL-12, and IFN-γ were also facilitated by compound-6. The correlation analysis showed a positive correlation between phagocytosis and the expression of TLR-2, iNOS, IL-6, IL-12. Collectively, the significant effect of compound-6, anti-melanization activity, antibiofilmand effective immunomodulant could be an interesting dual strategy drug agonist against cryptococcal meningitis.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Proteínas Opsonizantes/fisiologia , Fagocitose/efeitos dos fármacos , Animais , Antifúngicos/síntese química , Antifúngicos/química , Cápsulas Bacterianas/efeitos dos fármacos , Cápsulas Bacterianas/fisiologia , Células Cultivadas , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus/fisiologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/fisiologia , Furanos/síntese química , Furanos/química , Furanos/farmacologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Melaninas/metabolismo , Meningite Criptocócica/imunologia , Meningite Criptocócica/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Proteínas Opsonizantes/metabolismo
19.
Biochemistry (Mosc) ; 85(Suppl 1): S154-S176, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32087058

RESUMO

In this review, we present the data on the natural occurrence of chitin and its partially or fully deacetylated derivative chitosan, as well as their properties, methods of modification, and potential applications of derivatives with bactericidal, fungicidal, and antioxidant activities. The structure and physicochemical characteristics of the polymers, their functions, and features of chitin microbial synthesis and degradation, including the processes occurring in nature, are described. New data on the hydrolytic microorganisms capable of chitin degradation under extreme conditions are presented. Special attention is focused on the effect of physicochemical characteristics of chitosan, including molecular weight, degree of deacetylation, polydispersity index, and number of amino group derivatives (quaternized, succinyl, etc.) on the antimicrobial and antioxidant properties of modified polymers that can be of particular interest for biotechnology, medicine, and agriculture. Analysis of the available literature data confirms the importance of fundamental research to broaden our knowledge on the occurrence of chitin and chitosan in nature, their role in global biosphere cycles, and prospects of applied research aimed at using chitin, chitosan, and their derivatives in various aspects of human activity.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Quitosana/análogos & derivados , Quitosana/farmacologia , Fungicidas Industriais/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Bactérias/metabolismo , Biotecnologia , Quitosana/química , Quitosana/metabolismo , Proteção de Cultivos , Descoberta de Drogas , Fungicidas Industriais/química , Fungicidas Industriais/economia , Fungicidas Industriais/metabolismo , Humanos , Hidrólise , Peso Molecular , Polímeros
20.
PLoS One ; 15(2): e0228864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092072

RESUMO

The integration of metallic or ceramic nanoparticles in polymer matrices has improved the antimicrobial and antifungal behavior, resulting in the search for composites with increased bactericidal and antimycotic properties. A polycaprolactone fibers with copper oxide nanoparticles was prepared. Polycaprolactone-copper fibers (PCL- CuONPs) were prepared into two major steps in situ method: (a) Synthesis of CuO particles, then (b) incorporation of polycaprolactone to electrospun process. The first step is the reduction of Cu+2 ions by gallic acid in N,N-dimethylformamide and tetrahydrofuran solution with the simple addition of polycaprolactone in the solution for the second electrospun step. Raman spectra provide information about the nature of the copper oxide synthesized. There are three Raman peaks in the sample, at 294 and 581 cm-1 and a very broad band from 400 to 600 cm-1 which are characteristics bands for CuO. Scanning electron microscopy (TEM) revealed copper oxide nanoparticles with semispherical shapes with diameter 35 ±11 nm. Dynamic light scattering (DLS) analysis showed uniform CuONPs in a range of 88±11 nm. Scanning electron microscopy (SEM) of PCL-CuONps reveled fibers with diameters ranging from 925 to 1080 nm were successfully obtained by electrospinning technique. Orientation, morphology and diameter were influenced by the increment on CuONPs concentration, with the smaller diameter present in samples prepared from low concentrated solutions. The antimycotic applicability of the composite was evaluated to determine the antifungal activity in three species of the genus Candida (Candida albicans, Candida glabrata and Candida tropicalis). PCL-CuONPs exhibit a considerable antifungal effect on all species tested. The preparation of PCL-CuONPs was simple, fast and low-cost for practical application as an antifungal dressing.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Cobre/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/química , Candida/ultraestrutura , Cobre/administração & dosagem , Cobre/química , Humanos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanotecnologia , Poliésteres/química , Análise Espectral Raman
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA