RESUMO
Selecting the appropriate disinfectant to control and prevent healthcare-associated infections (HAIs) is a challenging task for environmental health experts due to the large number of available disinfectant products. This study aimed to develop a label-free flow cytometry (FCM) method for the rapid evaluation of bactericidal activity and to compare its efficacy with that of standard qualitative/quantitative suspension tests. The bactericidal efficiency of eight commercial disinfectants containing quaternary ammonium compounds (QACs) was evaluated against four strains recommended by EN 13727 (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus hirae) and four multidrug-resistant pathogens. The proposed FCM protocol measures changes in scattered light and counts following disinfectant exposure, neutralization, and culture steps. Unlike other available FCM-based methods, this approach does not rely on autofluorescence measurements, impedance cytometry, or fluorescent dyes. The FCM scattered light signals revealed both decreased count rates and morphological changes after treatment with minimum inhibitory concentrations (MICs) and higher concentrations for all tested bacteria. The results from the FCM measurements showed excellent correlation with those from standard assays, providing a rapid tool for monitoring the susceptibility profile of clinical, multidrug-resistant pathogens to chemical disinfectants, which could support infection prevention and control procedures for healthcare environments. This label-free FCM protocol offers a novel and rapid tool for environmental health experts, aiding in the optimization of disinfectant selection for the prevention and control of HAIs.
Assuntos
Desinfetantes , Citometria de Fluxo , Testes de Sensibilidade Microbiana , Desinfetantes/farmacologia , Citometria de Fluxo/métodos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacosRESUMO
The unprecedented increase in microbial resistance rates to all current drugs raises an acute need for the design of more effective antimicrobial strategies. Moreover, the importance of oxidative stress due to chronic inflammation in infections with resistant bacteria represents a key factor for the development of new antibacterial agents with potential antioxidant effects. Thus, the purpose of this study was to bioevaluate new O-aryl-carbamoyl-oxymino-fluorene derivatives for their potential use against infectious diseases. With this aim, their antimicrobial effect was evaluated using quantitative assays (minimum inhibitory/bactericidal/biofilms inhibitory concentrations) (MIC/MBC/MBIC), the obtained values being 0.156-10/0.312-10/0.009-1.25 mg/mL), while some of the involved mechanisms (i.e., membrane depolarization) were investigated by flow cytometry. The antioxidant activity was evaluated by studying the scavenger capacity of DPPH and ABTSâ¢+ radicals and the toxicity was tested in vitro on three cell lines and in vivo on the crustacean Artemia franciscana Kellog. The four compounds derived from 9H-fluoren-9-one oxime proved to exhibit promising antimicrobial features and particularly, a significant antibiofilm activity. The presence of chlorine induced an electron-withdrawing effect, favoring the anti-Staphylococcus aureus and that of the methyl group exhibited a +I effect of enhancing the anti-Candida albicans activity. The IC50 values calculated in the two toxicity assays revealed similar values and the potential of these compounds to inhibit the proliferation of tumoral cells. Taken together, all these data demonstrate the potential of the tested compounds to be further used for the development of novel antimicrobial and anticancer agents.
Assuntos
Anti-Infecciosos , Antioxidantes , Antioxidantes/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Candida albicans , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
The resistance of surfaces to biofouling remains a significant advantage for optical devices working in natural conditions, increasing their lifetime and reducing maintenance costs. This paper reports on the functionalities of transparent CeO2 thin films with thicknesses between 25 and 600 nm deposited by reactive magnetron sputtering on the glass substrate. The CeO2 photocatalytic performance exhibited an efficiency of 30% on imidacloprid degradation under 6 h of UV radiation and increased linearly with the irradiation time, suggesting a complete degradation within 48 h. The films did not alter the growth rate of the green algae Chlorella vulgaris after 72 h short-term exposure. The tested CeO2 films proved to efficiently inhibit with high efficiency the Staphylococcus aureus biofilms and planktonic growth (reducing the counts of bacterial cells by 2 to 8 logs), demonstrating the promising potential of these materials for obtaining antimicrobial and antibiofilm surfaces, with broad applications for the biomedical, ecological and industrial fields.
Assuntos
Cério , Chlorella vulgaris , Biofilmes , Cério/farmacologia , Cério/química , Staphylococcus aureusRESUMO
The efficient regioselective bromination and iodination of the nonsteroidal anti-inflammatory drug (NSAID) carprofen were achieved by using bromine and iodine monochloride in glacial acetic acid. The novel halogenated carprofen derivatives were functionalized at the carboxylic group by esterification. The regioselectivity of the halogenation reaction was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were screened for their in vitro antibacterial activity against planktonic cells and also for their anti-biofilm effect, using Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The cytotoxic activity of the novel compounds was tested against HeLa cells. The pharmacokinetic and pharmacodynamic profiles of carprofen derivatives, as well as their toxicity, were established by in silico analyses.
Assuntos
Bactérias Gram-Negativas , Bactérias Gram-Positivas , Antibacterianos/química , Antibacterianos/farmacologia , Carbazóis , Escherichia coli , Células HeLa , Humanos , Testes de Sensibilidade MicrobianaRESUMO
To investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population. From 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N = 344), nearby residents (living ≤ 300 m away from WWTPs; N = 431) and distant residents (living ≥ 1000 m away = reference group; N = 1165). We collected information on potential confounders via questionnaire. Culture of participants' stool samples was performed with ChromID®-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producing E. coli (ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure. Prevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.50) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.80-5.59) to be ESBL-EC carriers, when compared with distant residents. In stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage.
RESUMO
In an attempt to propose new applications for the biomedical field, complexes with mixed ligands {[Cu(bpy)2(µ2OClO3)]ClO4}n (1) and [Cu(phen)2(OH2)](ClO4)2 (2) (bpy: 2,2'-biyridine; phen and 1,10-phenantroline) were evaluated for their antibacterial and cytotoxicicity features and for the elucidation of some of the mechanisms involved. Complex (2) proved to be a very potent antibacterial agent, exhibing MIC and MBEC values 2 to 54 times lower than those obtained for complex (1) against both susceptible or resistant Gram-positive and Gram-negative strains, in planktonic or biofilm growth state. In exchange, complex (1) exhibited selective cytotoxicity against melanoma tumor cells (B16), proving a promising potential for developing novel anticancer drugs. The possible mechanisms of both antimicrobial and antitumor activity of the copper(II) complexes is their DNA intercalative ability coupled with ROS generation. The obtained results recommend the two complexes for further development as multipurpose copper-containing drugs.
Assuntos
Antineoplásicos , Complexos de Coordenação , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Quelantes/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Cristalografia por Raios X , LigantesRESUMO
Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp-both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.
Assuntos
Anti-Infecciosos , Quelantes , Complexos de Coordenação , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Pirimidinas , Saccharomyces cerevisiae/crescimento & desenvolvimento , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Linhagem Celular Tumoral , Quelantes/síntese química , Quelantes/química , Quelantes/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Humanos , Camundongos , Pirimidinas/síntese química , Pirimidinas/química , Pirimidinas/farmacologiaRESUMO
We report for the first time on the antimicrobial activity of MgB2 powders produced via the Reactive Liquid Infiltration (RLI) process. Samples with MgB2 wt.% ranging from 2% to 99% were obtained and characterized, observing different levels of grain aggregation and of impurity phases. Their antimicrobial activity was tested against Staphylococcus aureus ATCC BAA 1026, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. A general correlation is observed between the antibacterial activity and the MgB2 wt.%, but the sample microstructure also appears to be very important. RLI-MgB2 powders show better performances compared to commercial powders against microbial strains in the planktonic form, and their activity against biofilms is also very similar.
RESUMO
Pristine high-density bulk disks of MgB2 with added hexagonal BN (10 wt.%) were prepared using spark plasma sintering. The BN-added samples are machinable by chipping them into desired geometries. Complex shapes of different sizes can also be obtained by the 3D printing of polylactic acid filaments embedded with MgB2 powder particles (10 wt.%). Our present work aims to assess antimicrobial activity quantified as viable cells (CFU/mL) vs. time of sintered and 3D-printed materials. In vitro antimicrobial tests were performed against the bacterial strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecium DSM 13590, and Enterococcus faecalis ATCC 29212; and the yeast strain Candida parapsilosis ATCC 22019. The antimicrobial effects were found to depend on the tested samples and microbes, with E. faecium being the most resistant and E. coli the most susceptible.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Boro/farmacologia , Fungos/efeitos dos fármacos , Compostos de Magnésio/farmacologia , Candida parapsilosis/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Poliésteres/farmacologia , Impressão Tridimensional , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
We report on new biomaterials with promising bone and cartilage regeneration potential, from sustainable, cheap resources of fish origin. Thin films were fabricated from fish bone-derived bi-phasic calcium phosphate targets via pulsed laser deposition with a KrF * excimer laser source (λ = 248 nm, τFWHM ≤ 25 ns). Targets and deposited nanostructures were characterized by SEM and XRD, as well as by Energy Dispersive X-ray (EDX) and FTIR spectroscopy. Films were next assessed in vitro by dedicated cytocompatibility and antimicrobial assays. Films were Ca-deficient and contained a significant fraction of ß-tricalcium phosphate apart from hydroxyapatite, which could contribute to an increased solubility and an improved biocompatibility for bone regeneration applications. The deposited structures were biocompatible as confirmed by the lack of cytotoxicity on human gingival fibroblast cells, making them promising for fast osseointegration implants. Pulsed laser deposition (PLD) coatings inhibited the microbial adhesion and/or the subsequent biofilm development. A persistent protection against bacterial colonization (Escherichia coli) was demonstrated for at least 72 h, probably due to the release of the native trace elements (i.e., Na, Mg, Si, and/or S) from fish bones. Progress is therefore expected in the realm of multifunctional thin film biomaterials, combining antimicrobial, anti-inflammatory, and regenerative properties for advanced implant coatings and nosocomial infections prevention applications.
Assuntos
Osso e Ossos/química , Fosfatos de Cálcio/química , Materiais Revestidos Biocompatíveis/química , Peixes/metabolismo , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Biofilmes , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/farmacologia , Linhagem Celular , Infecção Hospitalar/prevenção & controle , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Humanos , Lasers , Teste de Materiais , Próteses e Implantes , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Oligoelementos/químicaRESUMO
Since the discovery of penicillin by Alexander Fleming in 1929 as a therapeutic agent against staphylococci, ß-lactam antibiotics (BLAs) remained the most successful antibiotic classes against the majority of bacterial strains, reaching a percentage of 65% of all medical prescriptions. Unfortunately, the emergence and diversification of ß-lactamases pose indefinite health issues, limiting the clinical effectiveness of all current BLAs. One solution is to develop ß-lactamase inhibitors (BLIs) capable of restoring the activity of ß-lactam drugs. In this review, we will briefly present the older and new BLAs classes, their mechanisms of action, and an update of the BLIs capable of restoring the activity of ß-lactam drugs against ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. Subsequently, we will discuss several promising alternative approaches such as bacteriophages, antimicrobial peptides, nanoparticles, CRISPR (clustered regularly interspaced short palindromic repeats) cas technology, or vaccination developed to limit antimicrobial resistance in this endless fight against Gram-negative pathogens.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , beta-Lactamases/metabolismo , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Animais , Bacteriófagos , Sistemas CRISPR-Cas , Carbapenêmicos/farmacologia , Enterobacter/efeitos dos fármacos , Enterobacter/enzimologia , Enterococcus/efeitos dos fármacos , Enterococcus/enzimologia , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Vacinação , Inibidores de beta-Lactamases/farmacologiaRESUMO
Complexes with mixed ligands [Cu(N-N)2(pmtp)](ClO4)2 ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenanthroline and pmpt: 5-phenyl-7-methyl-1,2,4-triazolo[1,5-a]pyrimidine) were synthesized and structurally and biologically characterized. Compound (1) crystallizes into space group Pa and (2) in P-1. Both complexes display an intermediate stereochemistry between the two five-coordinated ones. The biological tests indicated that the two compounds exhibited superoxide scavenging capacity, intercalative DNA properties, and metallonuclease activity. Tests on various cell systems indicated that the two complexes neither interfere with the proliferation of Saccharomyces cerevisiae or BJ healthy skin cells, nor cause hemolysis in the active concentration range. Nevertheless, the compounds showed antibacterial potential, with complex (2) being significantly more active than complex (1) against all tested bacterial strains, both in planktonic and biofilm growth state. Both complexes exhibited a very good activity against B16 melanoma cells, with a higher specificity being displayed by compound (1). Taken together, the results indicate that complexes (1) and (2) have specific biological relevance, with potential for the development of antitumor or antimicrobial drugs.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Complexos de Coordenação/química , Cobre/química , Compostos Heterocíclicos/química , Melanoma Experimental/tratamento farmacológico , Antibacterianos/química , Antineoplásicos/química , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , LigantesRESUMO
Aqueous chlorpromazine solutions exposed to 266â¯nm generated as fourth harmonic of Nd:YAG pulsed laser along time intervals from 1â¯min to 240â¯min were investigated for their antimicrobial activity against planktonic and adherent Gram-positive bacterial strains. Qualitative and quantitative assays based on microbiological methods and flow cytometry assays were performed to establish the minimum inhibitory and minimum biofilm eradication concentrations and to reveal some of the possible mechanisms of antimicrobial activity. Optimal irradiation conditions and combinations of photoproducts for achieving the best antimicrobial and antibiofilm effects are suggested. It was confirmed that chlorpromazine solutions irradiated for 15â¯min and 30â¯min have the best antimicrobial and antibiofilm activity against Staphylococcus aureus ATCC 6538, methicillin susceptible Staphylococcus aureus, methicillin resistant Staphylococcus aureus, Enterococcus faecium 17-VAR, Enterococcus faecalis 2921, and Bacillus subtilis 6633. Flow cytometry revealed that two of the possible mechanisms of the antimicrobial activity of irradiated chlorpromazine are the inhibition of efflux pumps activity and induction of cellular membrane lesions.
Assuntos
Biofilmes/efeitos dos fármacos , Clorpromazina/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Terapia com Luz de Baixa Intensidade/métodos , Citometria de Fluxo , Testes de Sensibilidade MicrobianaRESUMO
Two ZnO materials of spherical hierarchical morphologies, with hollow (ZnOHS) and solid cores (ZnOSS), were obtained through the hydrolysis of zinc acetylacetonate in 1,4-butanediol. The nature of the defects and surface reactivity for the two ZnO materials were investigated through photoluminescence, X-ray photoelectron spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy proving the coexistence of shallow and deep defects and, also, the presence of polyol byproducts adsorbed on the outer layers of the ZnO samples. The EPR spectroscopy coupled with the spin-trapping technique showed that the surface of the ZnO samples generates reactive oxygen species (ROS) like hydroxyl (â¢OH) and singlet oxygen (1O2) as well as carbon-centered radicals. The ZnO materials exhibited a wide spectrum of antimicrobial activity, being active against Gram-positive, Gram-negative, and fungi strains, both in planktonic and, more importantly, adherent growth states. The decrease of antimicrobial efficiency in the presence of a ROS scavenger (mannitol) and the decrease of the cell viability with the ROS level suggest that one of the mechanisms that governs both the antimicrobial and cytotoxic activities on human liver cells is ROS-mediated. However, at active antimicrobial concentrations, the biocompatibility of the tested materials is very good.
Assuntos
Antibacterianos/farmacologia , Nanoestruturas/química , Óxido de Zinco/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/toxicidade , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células Hep G2 , Humanos , Hidroxibutiratos/química , Radical Hidroxila/síntese química , Testes de Sensibilidade Microbiana , Nanoestruturas/toxicidade , Pentanonas/química , Oxigênio Singlete/química , Óxido de Zinco/síntese química , Óxido de Zinco/química , Óxido de Zinco/toxicidadeRESUMO
Five new copper(II) acrylate complexes (acr is the acrylate anion: C3H3O2) with imidazole derivatives (2-methylimidazole/2-MeIm, 5-methylimidazole/5-MeIm, 2-ethylimidazole/2-EtIm) of type: cis-[Cu(2-RIm)2(acr)2]·xH2O ((1): R = â»CH3, x = 2; (4): R = â»CH2â»CH3, x = 0), trans-[Cu(2-RIm)2(acr)2] ((2): R = â»CH3; (5): R = â»CH2â»CH3) and trans-[Cu(5-RIm)2(acr)2] ((3): R = â»CH3) have been prepared and characterized by elemental analysis, Fourier Transform Infrared spectrometry (FTIR), Electron Paramagnetic Resonance (EPR), electronic reflectance spectroscopy, scanning electron microscopy, and mass spectrometry. The single crystal X-ray diffraction study of complexes (2) and (5) reveals that the copper(II) ion is located on an inversion center and show elongated octahedral geometry completed by two coplanar bidentate acrylates and two unidentate imidazole derivatives displayed in trans positions. For complex (4) the single crystal X-ray diffraction shows that the copper(II) ion is in a distorted octahedral environment which can be easily confused with a trigonal prism completed by two bidentate acrylates and two unidentate imidazole derivatives displayed in cis positions. These results indicate the fact that complexes (4) and (5) are the geometric isomers of the same compound bis(acrylate)-bis(2-ethylimidazole)-copper(II). Complexes (1) and (2), as well as (4) and (5), were produced simultaneously in the reaction of the corresponding copper(II) acrylate with imidazole derivatives in methanol solution. Furthermore, in order to be able to formulate potential applications of the obtained compounds, our next goal was to investigate the in vitro antimicrobial activity of the synthesized complexes against Gram-positive and Gram-negative bacteria, as well as fungal strains, of both clinical and ecological importance (biodeterioration of historical buildings). The trans isomers (2) and (5), followed by (4) have shown the broadest range of antimicrobial activity. In case of (1) and (2) isomers, the trans isomer (2) was significantly more active than cis (1), while the cis isomer (4) proved to be more active than trans (5). Taken together, the biological evaluation results indicate that the trans (2) was the most active complex, demonstrating its potential for the development of novel antimicrobial agents, with potential applications in the biomedical and restoration of architectural monuments fields.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Cobre/química , Cobre/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Anti-Infecciosos/síntese química , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Ácidos Carboxílicos/síntese química , Cristalografia por Raios X , Fungos/efeitos dos fármacos , Ligação de Hidrogênio , Imidazóis/síntese química , Isomerismo , Ligantes , Testes de Sensibilidade Microbiana , Conformação MolecularRESUMO
The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, ß-pinene, eucalyptol, and limonene) and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol/ß-pinene/salicylic acid and eugenol/ß-pinene/2-phenoxyethanol/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC) values. The most active antimicrobial combination represented by salycilic acid/eugenol/ß-pinene/2-phenoxyethanol/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.
Assuntos
Acne Vulgar/prevenção & controle , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Plantas/química , Pele/efeitos dos fármacos , Acne Vulgar/microbiologia , Adolescente , Adulto , Monoterpenos Bicíclicos , Compostos Bicíclicos com Pontes/uso terapêutico , Cicloexanóis/uso terapêutico , Cicloexenos/uso terapêutico , Eucaliptol , Eugenol/uso terapêutico , Citometria de Fluxo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Limoneno , Testes de Sensibilidade Microbiana , Monoterpenos/uso terapêutico , Fitoterapia/métodos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Pele/microbiologia , Pele/patologia , Creme para a Pele/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Terpenos/uso terapêutico , Adulto JovemRESUMO
TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received increased attention. Two types of TiO2 nanoparticles co-doped with 1% of iron and nitrogen (TiO2-1% Fe-N) atoms were synthesized in hydrothermal conditions at pH of 8.5 (HT1) and 5.5 (HT2), and their antimicrobial activity and cytotoxic effects exerted on human pulmonary and dermal fibroblasts were assessed. These particles exhibited significant microbicidal and anti-biofilm activity, suggesting their potential application for microbial decontamination of different environments. In addition, our results demonstrated the biocompatibility of TiO2-1% Fe-N nanoparticles at low doses on lung and dermal cells, which may initiate oxidative stress through dose accumulation. Although no significant changes were observed between the two tested photocatalysts, the biological response was cell type specific and time- and dose-dependent; the lung cells proved to be more sensitive to nanoparticle exposure. Taken together, these experimental data provide useful information for future photocatalytic applications in the industrial, food, pharmaceutical, and medical fields.
Assuntos
Fibroblastos/metabolismo , Fibroblastos/microbiologia , Nanopartículas/química , Processos Fotoquímicos , Titânio/química , Citoesqueleto de Actina , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias , Catálise , Sobrevivência Celular/efeitos dos fármacos , Coloides , Humanos , Hidrodinâmica , Peroxidação de Lipídeos , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Difração de Raios XRESUMO
Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act as Sortase A inhibitors provided the starting point for identifying a new potential scaffold. Based on this template a series of new potential Sortase A inhibitors, that contain the 2-phenylthiazole moiety, were synthesized. The physicochemical characterisation confirmed the identity of the proposed structures. Antibacterial activity evaluation showed that the new compounds have a reduced activity against bacterial cell viability. However, the compounds prevent biofilm formation at very low concentrations, especially in the case of E. faecalis. Molecular docking studies performed estimate that this is most likely due to the inhibition of Sortase A. The new compounds could be used as add-on therapies together with known antibacterial agents in order to combat multidrug-resistance enterococcal infections.
Assuntos
Aminoaciltransferases/química , Proteínas de Bactérias/química , Cisteína Endopeptidases/química , Inibidores de Cisteína Proteinase/química , Tiazóis/química , Aminoaciltransferases/antagonistas & inibidores , Antibacterianos/química , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Biofilmes/efeitos dos fármacos , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/farmacologiaRESUMO
The rapid development of nanotechnology allowed the fabrication of a wide range of different nanomaterials, raising many questions about their safety and potential risks for the human health and environment. Most of the current nanotoxicology research is not standardized, hampering any comparison or reproducibility of the obtained results. Drosophotoxicology encompasses the plethora of methodological approaches addressing the use of Drosophila melanogaster as a choice organism in toxicology studies. Drosophila melanogaster model offers several important advantages, such as a relatively simple genome structure, short lifespan, low maintenance cost, readiness of experimental manipulation comparative to vertebrate models from both ethical and technical points of view, relevant gene homology with higher organisms, and ease of obtaining mutant phenotypes. The molecular pathways, as well as multiple behavioral and developmental parameters, can be evaluated using this model in lower, medium or high throughput type assays, allowing a systematic classification of the toxicity levels of different nanomaterials. The purpose of this paper is to review the current research on the applications of Drosophila melanogaster model for the in vivo assessment of nanoparticles toxicity and to reveal the huge potential of this model system to provide results that could enable a proper selection of different nanostructures for a certain biomedical application.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Nanopartículas/toxicidade , Animais , DNA/efeitos dos fármacos , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Sistemas de Liberação de Medicamentos , Humanos , Modelos Biológicos , Nanopartículas/químicaRESUMO
Growing resistance to antimicrobials, combined with pathogens that form biofilms, presents significant challenges in healthcare. Modifying current antimicrobial agents is an economical approach to developing novel molecules that could exhibit biological activity. Thus, five sulfanilamide Schiff bases were synthesized under microwave irradiation and characterized spectroscopically and in silico. They were evaluated for their antimicrobial and antibiofilm activities against both Gram-positive and Gram-negative bacterial strains. Their cytotoxic potential against two cancer cell lines was also determined. Gram-positive bacteria were susceptible to the action of these compounds. Derivatives 1b and 1d inhibited S. aureus's growth (MIC from 0.014 mg/mL) and biofilm (IC from 0.029 mg/mL), while compound 1e was active against E. faecalis's planktonic and sessile forms. Two compounds significantly reduced cell viability at 5 µg/mL after 24 h of exposure (1d-HT-29 colorectal adenocarcinoma cells, 1c-LN229 glioblastoma cells). A docking study revealed the increased binding affinities of these derivatives compared to sulfanilamide. Hence, these Schiff bases exhibited higher activity compared to their parent drug, with halogen groups playing a crucial role in both their antimicrobial and cytotoxic effects.