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1.
Chem Biodivers ; 17(1): e1900462, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31788939

RESUMO

A series of coumarin-tagged ß-lactam triazole hybrids (10a-10o) were synthesized and tested for their cytotoxic activity against MDA-MB-231 (triple negative breast cancer), MCF-7 (estrogen receptor positive breast cancer (ER+)) and A549 (human lung carcinoma) cancer cell lines including one normal cell line, HEK-293 (human embryonic kidney). Two compounds 10b and 10d exhibited substantial cytotoxic effect against MCF-7 cancer cell lines with IC50 values of 53.55 and 58.62 µm, respectively. More importantly, compounds 10b and 10d were non-cytotoxic against HEK-293 cell lines. Structure-activity relationship (SAR) studies suggested that the nitro and chloro group at the C-3 position of phenyl ring are favorable for anticancer activity, particularly against MCF-7 cell lines. Furthermore, antimicrobial evaluation of these compounds revealed modest inhibition of examined pathogenic strains with compounds 10c and 10i being the most promising antimicrobial agents against Pseudomonas aeruginosa and Candida albicans, respectively.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Cumarínicos/farmacologia , Triazóis/farmacologia , beta-Lactamas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Proliferação de Células/efeitos dos fármacos , Cumarínicos/síntese química , Cumarínicos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Relação Estrutura-Atividade , Triazóis/química , beta-Lactamas/química
2.
Microbiol Res ; 230: 126346, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31563763

RESUMO

In this study, we aimed to determine the interspecies interactions between Proteus mirabilis and Candida albicans. Mono and dual-species biofilms were grown in a microtiter plate and metabolomic analysis of the biofilms was performed. The effects of togetherness of two species on the expression levels of candidal virulence genes and urease and swarming activities of P.mirabilis were investigated. The growth of C.albicans was inhibited by P.mirabilis whereas the growth and swarming activity of P.mirabilis were increased by C.albicans. The inhibition of Candida cell growth was found to be biofilm specific. The alteration was not detected in urease activity. The expressions of EFG1, HWP1 and SAP2 genes were significantly down-regulated, however, LIP1 was upregulated by P.mirabilis. In the presence of P.mirabilis carbonhydrates, amino acids, polyamine and lipid metabolisms were altered in C.albicans. Interestingly, the putrescine level was increased up to 230 fold in dual-species biofilm compared to monospecies C.albicans biofilm. To our knowledge, this is the first study to investigate the impact of each microbial pathogen on the dual microbial environment by integration of metabolomic data.


Assuntos
Proteínas de Bactérias/metabolismo , Candida albicans/fisiologia , Proteus mirabilis/fisiologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Candida albicans/química , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Metabolômica , Proteus mirabilis/química , Proteus mirabilis/genética , Proteus mirabilis/crescimento & desenvolvimento
3.
Pol J Microbiol ; 68(3): 309-316, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31880876

RESUMO

Among the species belonging to the Aspergillus section Versicolores, Aspergillus creber has been poorly studied and still unexplored for its biological activities. The present study was undertaken to analyze A. creber extract and to evaluate its in vitro antimicrobial and anti-oxidant activities. UHPLC-MS/MS analysis of A. creber extract allowed the characterization of five known fungal metabolites including: asperlactone, emodin, sterigmatocystin, deoxybrevianamide E, and norsolorinic acid. The highest antimicrobial activity was displayed against Candida albicans, with a mean strongest inhibition zone of 20.6 ± 0.8 mm, followed by Gram-positive drug-resistant bacteria. The MIC values of A. creber extract varied from 0.325 mg/ml to 5 mg/ml. A. creber extract was shown a potent antioxidant activity and a high level of phenolic compounds by recording 89.28% scavenging effect for DPPH free radical, 92.93% in ABTS assay, and 85.76 mg gallic acid equivalents/g extract in Folin-Ciocalteu assay. To our knowledge, this is the first study concerning biological and chemical activities of A. creber species. Based on the obtained results, A. creber could be a promising source of natural antimicrobial and antioxidant compounds.Among the species belonging to the Aspergillus section Versicolores, Aspergillus creber has been poorly studied and still unexplored for its biological activities. The present study was undertaken to analyze A. creber extract and to evaluate its in vitro antimicrobial and anti-oxidant activities. UHPLC-MS/MS analysis of A. creber extract allowed the characterization of five known fungal metabolites including: asperlactone, emodin, sterigmatocystin, deoxybrevianamide E, and norsolorinic acid. The highest antimicrobial activity was displayed against Candida albicans, with a mean strongest inhibition zone of 20.6 ± 0.8 mm, followed by Gram-positive drug-resistant bacteria. The MIC values of A. creber extract varied from 0.325 mg/ml to 5 mg/ml. A. creber extract was shown a potent antioxidant activity and a high level of phenolic compounds by recording 89.28% scavenging effect for DPPH free radical, 92.93% in ABTS assay, and 85.76 mg gallic acid equivalents/g extract in Folin-Ciocalteu assay. To our knowledge, this is the first study concerning biological and chemical activities of A. creber species. Based on the obtained results, A. creber could be a promising source of natural antimicrobial and antioxidant compounds.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Aspergillus/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Espectrometria de Massas em Tandem
4.
BMC Complement Altern Med ; 19(1): 303, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703673

RESUMO

BACKGROUND: Candida albicans is an opportunistic pathogen that causes oral candidiasis and denture stomatitis. It has also been reported to infect oral mucositis lesions in patients who suffer from cancer affecting the head and neck and who receive chemotherapy and radiotherapy treatments. This study aimed to investigate the effects of two cinnamon bark fractions, i.e., an essential oil and an aqueous extract enriched in proanthocyanidins (Cinnulin PF®) on growth, biofilm formation, and adherence properties of C. albicans as well as on oral epithelial cells (barrier integrity, inflammatory response). METHODS: A microplate dilution assay was used to determine antifungal and anti-biofilm properties. A fluorescent assay was used to determine C. albicans adherence to oral epithelial cells. Cytotoxicity toward oral epithelial cells was assessed by determination of cell metabolic activity. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. IL-6 and IL-8 secretion by TNFα-stimulated oral epithelial cells was quantified by ELISA. RESULTS: While Cinnulin PF® did not reduce C. albicans growth, the cinnamon bark oil exhibited high antifungal activity with minimum inhibitory concentrations and minimum fungicidal concentrations in the range of 0.039 to 0.078%. The cinnamon oil was also active against a pre-formed C. albicans biofilm. Interestingly, Cinnulin PF® prevented biofilm formation by C. albicans and attenuated its adherence to oral epithelial cells. At their effective concentrations, the cinnamon oil and the Cinnulin PF® displayed no significant cytotoxicity against oral epithelial cells. In an in vitro model, both cinnamon fractions reinforced the integrity of the oral epithelial barrier. Lastly, Cinnulin PF® inhibited the secretion of interleukin-6 and interleukin-8 by oral epithelial cells stimulated with TNF-α. CONCLUSION: By their ability to attenuate growth, biofilm formation and adherence property of C. albicans, to reinforce the epithelial barrier function, and to exert anti-inflammatory properties the two cinnamon fractions (essential oil, Cinnulin PF®) investigated in the present study may be promising agents for treating oral infections involving C. albicans.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/microbiologia , Cinnamomum zeylanicum/química , Células Epiteliais/microbiologia , Boca/microbiologia , Óleos Voláteis/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Candidíase Bucal/tratamento farmacológico , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Boca/metabolismo , Casca de Planta/química
5.
J Agric Food Chem ; 67(47): 13033-13039, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31730339

RESUMO

Three new macrocyclic trichothecenes possessing rare 6'-ketal moieties, roridoxins A-C (1-3), and five known compounds (4-8) were isolated from the insect-associated fungus Myrothecium roridum. Their structures were confirmed by a combination of NMR and HRESIMS data, while their absolute configurations were unambiguously determined by single-crystal X-ray analysis and electronic circular dichroism experiments. Trichothecenes 1 and 3 showed potent antifungal activities against four strains of phytopathogenic fungi. In addition, 1, 3, 5, and 6 were found to significantly inhibit the cell growth of Candida albicans with minimal inhibitory concentration values from 8.8 to 18.5 µg/mL. Moreover, they were able to inhibit the biofilm formation of C. albicans better than the positive control.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Hypocreales/química , Insetos/microbiologia , Tricotecenos/química , Tricotecenos/farmacologia , Animais , Antifúngicos/metabolismo , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Hypocreales/isolamento & purificação , Hypocreales/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tricotecenos/metabolismo
6.
Int J Mol Sci ; 20(20)2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614738

RESUMO

The essential role of dolichyl phosphate (DolP) as a carbohydrate carrier during protein N-glycosylation is well established. The cellular pool of DolP is derived from de novo synthesis in the dolichol branch of the mevalonate pathway and from recycling of DolPP after each cycle of N-glycosylation, when the oligosaccharide is transferred from the lipid carrier to the protein and DolPP is released and then dephosphorylated. In Saccharomyces cerevisiae, the dephosphorylation of DolPP is known to be catalyzed by the Cwh8p protein. To establish the role of the Cwh8p orthologue in another distantly related yeast species, Candida albicans, we studied its mutant devoid of the CaCWH8 gene. A double Cacwh8∆/Cacwh8∆ strain was constructed by the URA-blaster method. As in S. cerevisiae, the mutant was impaired in DolPP recycling. This defect, however, was accompanied by an elevation of cis-prenyltransferase activity and higher de novo production of dolichols. Despite these compensatory changes, protein glycosylation, cell wall integrity, filamentous growth, and biofilm formation were impaired in the mutant. These results suggest that the defects are not due to the lack of DolP for the protein N-glycosylation but rather that the activity of oligosacharyltransferase could be inhibited by the excess DolPP accumulating in the mutant.


Assuntos
Candida albicans/metabolismo , Proteínas Fúngicas/genética , Oligossacarídeos de Poli-Isoprenil Fosfato/metabolismo , Processamento de Proteína Pós-Traducional , Pirofosfatases/genética , Candida albicans/crescimento & desenvolvimento , Parede Celular/metabolismo , Proteínas Fúngicas/metabolismo , Glicosilação , Morfogênese , Pirofosfatases/metabolismo
7.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31527130

RESUMO

Candida-associated denture stomatitis (DS) is a persistent and chronic oral infection of the denture-bearing palatal mucosa. DS stems from the ability of the fungal opportunistic pathogen Candida albicans to adhere to denture material and invade palatal tissue. Although DS is the most prevalent form of oral candidiasis, there are currently no feasible therapeutic strategies for the prevention of this recurrent condition. We developed a peptide-based antimicrobial bioadhesive formulation specifically designed for oral topical formulation. In this study, we aimed to evaluate the applicability of the novel formulation for the prevention of C. albicans colonization on denture material and development of clinical disease. To that end, using the latest technological advances in dental digital design and three-dimensional (3D) printing, we fabricated an intraoral device for rats with universal fit. The device was successfully installed and used to develop clinical DS. Importantly, by taking a preventative therapeutic approach, we demonstrated the potential clinical utility of the novel formulation as a safe and feasible prophylactic agent against DS.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/prevenção & controle , Cimentos Dentários/farmacologia , Estomatite sob Prótese/prevenção & controle , Animais , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Cimentos Dentários/química , Dentaduras/microbiologia , Modelos Animais de Doenças , Masculino , Mucosa Bucal/microbiologia , Ratos , Ratos Sprague-Dawley , Estomatite sob Prótese/tratamento farmacológico , Estomatite sob Prótese/microbiologia
8.
Molecules ; 24(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540285

RESUMO

Studies on the functionalization of materials used for the construction of filtering facepiece respirators (FFRs) relate to endowing fibers with biocidal properties. There is also a real need for reducing moisture content accumulating in such materials during FFR use, as it would lead to decreased microorganism survival. Thus, in our study, we propose the use of superabsorbent polymers (SAPs), together with a biocidal agent (biohalloysite), as additives in the manufacturing of polypropylene/polyester (PP/PET) multifunctional filtering material (MFM). The aim of this study was to evaluate the MFM for stability of the modifier's attachment to the polymer matrix, the degree of survival of microorganisms on the nonwoven, and its microorganism filtration efficiency. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were used to test the stability of the modifier's attachment. The filtration efficiency was determined under conditions of dynamic aerosol flow of S. aureus bacteria. The survival rates (N%) of the following microorganisms were assessed: Escherichia coli and Staphylococcus aureus bacteria, Candida albicans yeast, and Aspergillus niger mold using the AATCC 100-2004 method. FTIR spectrum analysis confirmed the pre-established composition of MFM. The loss of the active substance from MFM in simulated conditions of use did not exceed 0.02%, which validated the stability of the modifier's attachment to the PP/PET fiber structure. SEM image analysis verified the uniformity of the MFM structure. Lower microorganism survival rates were detected for S. aureus, C. albicans, and E. coli on the MFM nonwoven compared to control samples that did not contain the modifiers. However, the MFM did not inhibit A. niger growth. The MFM also showed high filtration efficiency (99.86%) against S. aureus bacteria.


Assuntos
Desinfetantes/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Polipropilenos/síntese química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Desinfetantes/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Filtração/instrumentação , Microscopia Eletrônica de Varredura , Polímeros , Polipropilenos/química , Dispositivos de Proteção Respiratória/microbiologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
9.
Mater Sci Eng C Mater Biol Appl ; 105: 110055, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546416

RESUMO

Designing of mechanically tough elastomeric materials encompassed with intrinsic surface hydrophobicity, antistatic and antimicrobial attributes is in skyrocketing demands, especially to protect the instruments which are submerged in water. Herein, the authors depicted the fabrication of interpenetrating polymer network-based nanocomposites containing different doses of octadecylamine capped Cu/RGO nanohybrid. The structures and morphologies of the synthesized nanohybrid and the fabricated nanocomposites were characterized by using FTIR, XRD, XPS, TGA, FESEM and TEM analyses. Most interestingly the nanocomposites showed good hydrophobicity (static contact angle: 119.2°-129.3°), low surface resistivity (~107 Ω m) and strong antimicrobial activity towards Gram negative (Pseudomonas aeruginosa and Yersinia pestis) and Gram positive (Bacillus cereus) bacterial strains. The fabricated nanocomposites also exhibited antifungal (Candida albicans) activity. In addition, the fabricated nanocomposites showed excellent mechanical properties including high tensile strength (14.03-20.9 MPa), outstanding flexibility (1887-2470%), excellent toughness (249.89-510.1 MJ.m-3), high scratch resistance (>10 kg) and high thermostability (281-288 °C). Therefore, the fabricated nanocomposites can be used as an effective thin film for many advanced applications.


Assuntos
Aminas , Anti-Infecciosos , Substâncias Antieletricidade Estática , Bactérias/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Cobre , Grafite , Nanocompostos , Aminas/química , Aminas/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Substâncias Antieletricidade Estática/química , Substâncias Antieletricidade Estática/farmacologia , Cobre/química , Cobre/farmacologia , Grafite/química , Grafite/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Nanocompostos/química , Nanocompostos/uso terapêutico , Oxirredução
10.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470665

RESUMO

Fungal infection is a leading cause of mortality in immunocompromised population; thus, it is urgent to develop new and safe antifungal agents. Different from human cells, fungi have a cell wall, which is composed mainly of polysaccharide glucan and chitin. The unique cell wall structure is an ideal target for antifungal drugs. In this research, a chemical-genetic method was used to isolate antifungal agents that target chitin synthesis in yeast cells. From a compound library, we isolated two benzothiazole compounds that showed greater toxicity to yeast mutants lacking glucan synthase Fks1 compared to wild-type yeast cells and mutants lacking chitin synthase Chs3. Both of them inhibited the activity of chitin synthase in vitro and reduced chitin level in yeast cells. Besides, these compounds showed clear synergistic antifungal effect with a glucan synthase inhibitors caspofungin. Furthermore, these compounds inhibited the growth of Saccharomyces cerevisiae and opportunistic pathogen Candida albicans. Surprisingly, the genome-wide mass-spectrometry analysis showed decreased protein level of chitin synthases in cells treated with one of these drugs, and this decrease was not a result of downregulation of gene transcription. Therefore, we successfully identified two new antifungal agents that inhibit chitin synthesis using a chemical-genetic method.


Assuntos
Antifúngicos/farmacologia , Benzotiazóis/farmacologia , Candida albicans/efeitos dos fármacos , Quitina Sintase/genética , Quitina/antagonistas & inibidores , Equinocandinas/genética , Regulação Fúngica da Expressão Gênica , Glucosiltransferases/genética , Proteínas de Membrana/genética , Proteínas de Saccharomyces cerevisiae/genética , Antifúngicos/química , Benzotiazóis/química , Candida albicans/enzimologia , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Caspofungina/farmacologia , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Quitina/biossíntese , Quitina Sintase/antagonistas & inibidores , Quitina Sintase/deficiência , Combinação de Medicamentos , Descoberta de Drogas , Sinergismo Farmacológico , Equinocandinas/antagonistas & inibidores , Equinocandinas/deficiência , Perfilação da Expressão Gênica , Glucosiltransferases/antagonistas & inibidores , Glucosiltransferases/deficiência , Ensaios de Triagem em Larga Escala , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/deficiência , Testes de Sensibilidade Microbiana , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
11.
Diagn Microbiol Infect Dis ; 95(3): 114863, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471074

RESUMO

It is known that synergy between Candida albicans and Staphylococcus aureus results in enhanced biofilm formation and increased resistance to antimicrobials. Ceragenins (CSAs) are derivatives of cholic acid designed to mimic the antimicrobial activities of endogenous antimicrobial peptides. In this study, various CSAs were tested on C. albicans and methicillin-susceptible S. aureus or methicillin-resistant S. aureus mono or multispecies biofilms at 2 different concentrations (16 and 64 µg/mL) and compared with conventional antimicrobials. CSA-8 was active agent both with mono and multispecies biofilms (P < 0.05). Among antifungals, amphotericin B and, among antibacterials, ciprofloxacin and gentamicin were active agents against all studied microorganisms. This study suggests that CSAs, especially CSA-8, have useful antibiofilm effects against monomicrobial or fungal-bacterial multispecies biofilms.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Esteroides/farmacologia , Biofilmes/crescimento & desenvolvimento , Técnicas de Cocultura , Contagem de Colônia Microbiana , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Estrutura Molecular , Esteroides/química
12.
ACS Appl Mater Interfaces ; 11(38): 34676-34687, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483991

RESUMO

Nanoparticle-cell interactions between silica nanomaterials and mammalian cells have been investigated extensively in the context of drug delivery, diagnostics, and imaging. While there are also opportunities for applications in infectious disease, the interactions of silica nanoparticles with pathogenic microbes are relatively underexplored. To bridge this knowledge gap, here, we investigate the effects of organosilica nanoparticles of different sizes, concentrations, and surface coatings on surface association and viability of the major human fungal pathogen Candida albicans. We show that uncoated and PEGylated organosilica nanoparticles associate with C. albicans in a size and concentration-dependent manner, but on their own, do not elicit antifungal activity. The particles are also shown to associate with human white blood cells, in a similar trend as observed with C. albicans, and remain noncytotoxic toward neutrophils. Smaller particles are shown to have low association with C. albicans in comparison to other sized particles and their association with blood cells was also observed to be minimal. We further demonstrate that by chemically immobilizing the clinically important echinocandin class antifungal drug, caspofungin, to PEGylated nanoparticles, the cell-material interaction changes from benign to antifungal, inhibiting C. albicans growth when provided in high local concentration on a surface. Our study provides the foundation for defining how organosilica particles could be tailored for clinical applications against C. albicans. Possible future developments include designing biomaterials that could detect, prevent, or treat bloodstream C. albicans infections, which at present have very high patient mortality.


Assuntos
Antifúngicos , Candida albicans/crescimento & desenvolvimento , Materiais Revestidos Biocompatíveis , Nanopartículas , Neutrófilos/metabolismo , Compostos de Organossilício , Polietilenoglicóis , Antifúngicos/química , Antifúngicos/farmacologia , Candidíase/tratamento farmacológico , Candidíase/metabolismo , Candidíase/patologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia
13.
BMC Complement Altern Med ; 19(1): 247, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488126

RESUMO

BACKGROUND: With the current concern caused by drug resistant microorganisms, alternatives to traditional antimicrobials are increasingly necessary. Historical holistic treatments involving natural approaches are now of interest as a potential alternative. Many essential oils have antimicrobial properties with the ability to modify bacterial and fungal population dynamics in low concentrations. METHODS: In this study, bacterial and fungal growth in response to varying concentrations of arborvitae oil was assessed using spectrophotometric methods to obtain estimates of population growth parameters including carrying capacity (K) and intrinsic rate of growth (r). Estimates of these parameters were compared among doses within strains using general linear modeling. RESULTS: Results suggest the active component of the essential oil arborvitae is likely of hydrophilic nature and demonstrates the ability to influence both K and r during bacterial and fungal growth in a dose-dependent manner. Highly concentrated doses of arborvitae completely kill Escherichia coli and significantly inhibit Staphylococcus aureus, however these same doses have no effect on Pseudomonas aeruginosa. Accordingly, microdoses of arborvitae demonstrated the ability to inhibit population growth parameters in both prokaryotic and eukaryotic microorganisms. Specifically, K of E. coli, r of Candida auris, and both K and r of Candida albicans were significantly reduced in the presence of microdoses of arborvitae. CONCLUSIONS: Microdoses of essential oils have the ability to inhibit one or both population parameters in both prokaryotic and eukaryotic microorganisms. Some microorganisms appear to be more susceptible to this essential oil arborvitae than other microorganisms. The use of essential oils, such as arborvitae, as novel antimicrobials may prove useful when contending with the current epidemic of multidrug resistant pathogens.


Assuntos
Óleos Voláteis/farmacologia , Thuja/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Óleos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
14.
Curr Drug Deliv ; 16(7): 645-653, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31362675

RESUMO

BACKGROUND: Amphotericin B (AmB) is important for the treatment of systemic fungal infections. Nowadays, only intravenous administration (IV) of AmB has been available due to its low aqueous solubility. Two forms of AmB are available. The first is Fungizone®, a mixture of AmB and sodium deoxcycholate that produces severe nephrotoxicity. The second are lipid-based formulations that reduce nephrotoxicity, but they are costly and require higher dose than Fungizone®. Thus, a cheaper delivery system with reduced AmB toxicity is required. OBJECTIVE: To develop and characterize AmB loaded-nanostructured lipid carriers (AmB-loaded NLCs) for IV administration to reduce AmB toxicity. METHODS: AmB-loaded NLCs with different solid lipids were prepared by the high-pressure homogenization technique. Their physicochemical properties and the drug release profile were examined. The molecular structure of AmB, antifungal and hemolysis activities of developed AmB-loaded NLCs were also evaluated. RESULTS: AmB-loaded NLCs ~110 to ~140 nm in diameter were successfully produced with a zeta potential of ~-19 mV and entrapment efficiency of ~75%. In vitro release showed fast release characteristics. AmB-loaded NLCs could reduce the AmB molecular aggregation as evident from the absorbance ratio of the first to the fourth peak showing a partial aggregation of AmB. This result suggested that AmB-loaded NLCs could offer less nephrotoxicity compared to Fungizone®. In vitro antifungal activity of AmB-loaded NLCs showed a minimum inhibitory concentration of 0.25 µgmL-1. CONCLUSION: AmB-loaded NLCs present high potential carriers for effective IV treatment with prolonged circulation time and reduced toxicity.


Assuntos
Anfotericina B , Antifúngicos , Portadores de Fármacos , Nanoestruturas , Administração Intravenosa , Anfotericina B/administração & dosagem , Anfotericina B/química , Anfotericina B/toxicidade , Animais , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/toxicidade , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/toxicidade , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/toxicidade , Ovinos
15.
Med Sci Monit Basic Res ; 25: 179-186, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31451678

RESUMO

BACKGROUND With the continued demand for new, effective, and safe endodontic therapies, the aim of this study was assessment of efficiency of the ethyl acetate (EthOAc) extract of Tanacetum vulgare (L.) against Candida albicans. MATERIAL AND METHODS The antifungal effectiveness of the EthOAc extract of T. vulgare was determined using the agar disk diffusion method. The inhibition zones induced by the EthOAc extract were compared after 5 minutes, 60 minutes, and 24 hours to those induced by standard solutions (2% chlorhexidine, saturated calcium hydroxide, and 2% sodium hypochlorite). Statistical analysis of the results was performed using the Kruskal-Wallis test and one-way ANOVA. RESULTS The inhibition zone of chlorhexidine against C. albicans was 30.3-19.3 mm, but in combination with EthOAc extract (100 mg/mL) of T. vulgare, this inhibition was from 32.7-30 mm, indicating that this combination exerted a marked synergistic effect against C. albicans. The inhibition zone of sodium hypochlorite (69.7-65 mm) was higher than the inhibition zone of EthOAc extract and chlorhexidine. The combination of EthOAc extract with sodium hypochlorite resulted in a loss of antifungal activity. Furthermore, the activity of the EthOAc extract against C. albicans was decreased after mixing the extract with dentine at a concentration of 25 mg/50 µL (30.3-20.7 mm). The EthOAc extract did not show a genotoxic effect on lymphocyte cells. CONCLUSIONS The EthOAc extract of T. vulgare may be a useful tool to discover natural bioactive agents that have antifungal activity against C. albicans and could be used as endodontic therapies.


Assuntos
Acetatos/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tanacetum/química , Candida albicans/crescimento & desenvolvimento , Dentina/metabolismo , Sinergismo Farmacológico , Humanos , Linfócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mutagênicos/toxicidade
16.
J Coll Physicians Surg Pak ; 29(9): 828-832, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31455476

RESUMO

OBJECTIVE: To determine the growth of microorganisms in propofol when combined with fentanyl and lidocaine in different temperatures and times in order to find out whether there is any improvement in antimicrobial effect to lengthen the safe duration of time for application of propofol. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Istanbul Aydin University Laboratory, Istanbul, Turkey, from June to September 2018. METHODOLOGY: The studied drugs and thier combination was used to determine their effect on bacterial growth of Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Acinetobacter baumanni. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1:100 concentration. Colony numbers were measured as colony forming units mL-1 at 0, 8, and 24 hours and at 4oC, 22oC and 37oC. RESULTS: In general, propofol supported the growth of microorganisms. Fentanyl with propofol also promoted the growth, especially in room and body temperature at 8th and 24th hours but when combined with lidocaine, the number of CFUs was reduced significantly compared with propofol + fentanyl group. Lidocaine inhibited the growth of microorganisms in all the solutions except for candida albicans. CONCLUSION: Lidocaine was shown to have antibacterial effect which carries advantage for inhibiting infections due to propofol; but aseptic technique is essential during preparation of propofol infusions. Fentanyl like propofol also promoted the growth at room and body temperatures.


Assuntos
Acinetobacter baumannii/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Fentanila , Lidocaína , Propofol , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Anestésicos , Contagem de Colônia Microbiana , Armazenamento de Medicamentos , Temperatura Ambiente , Fatores de Tempo , Turquia
17.
J Med Microbiol ; 68(10): 1497-1506, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31460860

RESUMO

Aim. The aim of this work was to characterize the response of Candida albicans to atorvastatin, and to assess its in vivo antifungal capability.Methodology. The effect of atorvastatin on the growth and viability of C. albicans was assessed. The ability of the statin to alter cell permeability was quantified by measuring amino acid and protein leakage. The response of C. albicans to atorvastatin was assessed using label-free quantitative proteomics. The in vivo antifungal activity of atorvastatin was assessed using Galleria mellonella larvae infected with C. albicans.Results. Atorvastatin inhibited the growth of C. albicans. The atorvastatin-treated cells showed lower ergosterol levels than the controls, demonstrated increased calcofluor staining and released elevated quantities of amino acids and protein. Larvae infected with C. albicans showed a survival rate of 18.1±4.2 % at 144 h. In contrast, larvae administered atorvastatin (9.09 mg kg-1) displayed a survival rate of 60.2±6.4 % (P<0.05). Label-free quantitative proteomics identified 1575 proteins with 2 or more peptides and 465 proteins were differentially abundant (P<0.05). There was an increase in the abundance of enzymes with oxidoreductase and hydrolase activity in atorvastatin-treated cells, and squalene monooxygenase (4.52-fold increase) and lanosterol synthase (2.84-fold increase) were increased in abundance. Proteins such as small heat shock protein 21 (-6.33-fold) and glutathione peroxidase (-2.05-fold) were reduced in abundance.Conclusion. The results presented here indicate that atorvastatin inhibits the growth of C. albicans and is capable of increasing the survival of G. mellonella larvae infected with C. albicans.


Assuntos
Antifúngicos/farmacologia , Atorvastatina/farmacologia , Candida albicans/efeitos dos fármacos , Animais , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Candidíase/microbiologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Larva/microbiologia , Mariposas/microbiologia
18.
Future Microbiol ; 14: 839-846, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31373210

RESUMO

Aim: The primary objective of this study was to evaluate the effects of polypeptide-enriched Gastrodia elata extracts (GE) on vulvovaginal candidiasis (VVC). Materials & methods: A VVC model induced by Candida albicans (C. albicans) infection was successfully developed in BALB/c mice. After treatment, the colony-forming unit (CFU) of vaginal lavage was measured by plating. The extent of the inflammatory response was assessed by hematoxylin-eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Results: GE had an inhibitory effect on the proliferation of C. albicans and inflammatory reaction. Meanwhile, it had a potentially beneficial effect on the growth of Lactobacillus. Conclusion: These results showed the potential application of GE as an antifungal agent in VVC treatment.


Assuntos
Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Gastrodia/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/crescimento & desenvolvimento , Candidíase Vulvovaginal/sangue , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Modelos Animais de Doenças , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucinas/sangue , Interleucinas/metabolismo , Camundongos Endogâmicos BALB C , Peptídeos/química , Resultado do Tratamento , Vagina/metabolismo , Vagina/microbiologia , Vagina/patologia
19.
Molecules ; 24(16)2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426323

RESUMO

Dermaseptins belonging to a large family of cationic membrane-disruption antimicrobial peptides display extensive antibacterial and antiproliferative activities depending on a coil-to-helix transition and the specific structural parameters. Herein, a novel dermaseptin peptide named Der-PS4 was discovered from the skin secretion of the waxy monkey tree frog, Phyllomedusa sauvagii. The complementary DNA (cDNA)-encoding precursor was obtained relying on "shotgun" cloning, and afterwards, a mature peptide amino acid sequence was identified by reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS. Specimens were chemically synthesized and applied for further functional studies. Structural analysis demonstrated a higher α-helical content in the membrane-mimetic environment compared with that in the ammonium acetate/water circumstance. Der-PS4 displayed a broad spectrum of antimicrobial activities against tested pathogenic microorganisms, however, exhibiting slight membrane-damaging effectiveness towards horse red blood cells. Coincident with the inhibitory activities on pathogens, Der-PS4 also showed considerable biofilm eradicating impact. Also, Der-PS4 penetrated cell membrane in a relative short period under each minimum bactericidal concentration. In addition, Der-PS4 possessed antiproliferative capacity against five cancer cell lines, while presenting slight suppressing effect on human microvascular endothelial, HMEC-1. These findings provide a promising insight for the discovery and development of novel drugs from a natural source.


Assuntos
Proteínas de Anfíbios/farmacologia , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Proteínas Recombinantes/farmacologia , Sequência de Aminoácidos , Proteínas de Anfíbios/química , Proteínas de Anfíbios/isolamento & purificação , Proteínas de Anfíbios/metabolismo , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/metabolismo , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Anuros/fisiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Clonagem Molecular/métodos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Expressão Gênica , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Hemólise/efeitos dos fármacos , Cavalos , Humanos , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Pele/química
20.
J Appl Microbiol ; 127(5): 1362-1372, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31297951

RESUMO

AIM: The increase in the number of fungal infections worldwide, coupled with the limitations of current antifungal chemotherapy, demand the development of safe and effective new antifungals. Here, we presented the synthesis of a novel acridone (M14) and its antifungal properties against Candida and dermatophytes species. METHODS AND RESULTS: A series of 17 acridones was designed, synthesized and tested for its antifungal activity. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Only the acridone M14 showed growth-inhibitory activity against reference strains and clinical isolates of Candida and dermatophytes, with MIC range of 7·81-31·25 µg ml-1 . Moreover, M14 exhibited fungicidal activity and prevented biofilm formation by C. albicans as well as reduced the viability of preformed biofilms, even at sub-MICs. The confocal laser scanning microscopy analysis revealed that C. albicans hyphal growth was completely inhibited in the presence of M14. Similarly, there was a severe inhibition on hyphal growth of Trichophyton rubrum. We also found that M14 has relatively low toxicity to human fibroblasts. CONCLUSIONS: The new acridone M14 has antifungal properties against Candida spp. and dermatophytes, and antibiofilm activity against C. albicans. In addition, M14 is relatively selective to fungal cells compared to human normal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its in vitro antifungal activity, anti-Candida biofilm effect and moderate cytotoxicity towards normal human cell, M14 may serve as a valuable lead compound to develop a new antifungal agent.


Assuntos
Acridonas/farmacologia , Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Acridonas/síntese química , Antifúngicos/síntese química , Biofilmes/crescimento & desenvolvimento , Candida/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Sobrevivência Celular , Humanos , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Trichophyton/efeitos dos fármacos , Trichophyton/crescimento & desenvolvimento
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