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1.
Chem Biodivers ; : e202400786, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38777789

ABSTRACT

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50>40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5 % was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.

2.
Chem Biodivers ; 21(4): e202400063, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38329295

ABSTRACT

The xanthone lichenxanthone did not show toxic effects (LC50>1.0 mg/mL). lichenxanthone prevented nociceptive behavior induced by acidic saline, and its analgesic effect was blocked by amiloride, highlighting the involvement of neuromodulation of acid-sensitive ion channels (ASICs). In the analysis of anti-inflammatory activity, concentrations of 0.1 and 0.5 mg/mL of lichenxanthone reduced the edema induced by k-carrageenan 3.5 %, observed from the fourth hour of analysis. This effect was similar to that observed with ibuprofen (positive control). No leukocyte infiltrates were observed in lichenxanthone, suggesting that the compound acts in the acute inflammatory response. The results of the molecular docking study revealed that lichenxanthone exhibited better affinity energy when compared to the ibuprofen control against the two targets evaluated.


Subject(s)
Ibuprofen , Zebrafish , Animals , Molecular Docking Simulation , Anti-Inflammatory Agents/pharmacology , Ion Channels
3.
Future Microbiol ; 19: 91-106, 2024 01.
Article in English | MEDLINE | ID: mdl-38294293

ABSTRACT

Background: Staphylococcus aureus is a human pathogen responsible for high mortality rates. The development of new antimicrobials is urgent. Materials & methods: The authors evaluated the activity of hydralazine along with its synergism with other drugs and action on biofilms. With regard to action mechanisms, the authors evaluated cell viability, DNA damage and molecular docking. Results: MIC and minimum bactericidal concentration values ranged from 128 to 2048 µg/ml. There was synergism with oxacillin (50%) and vancomycin (25%). Hydralazine reduced the viability of biofilms by 50%. After exposure to hydralazine 2× MIC, 58.78% of the cells were unviable, 62.07% were TUNEL positive and 27.03% presented damage in the comet assay (p < 0.05). Hydralazine showed affinity for DNA gyrase and TyrRS. Conclusion: Hydralazine is a potential antibacterial.


Staphylococcus aureus is a bacterium that can cause infection. Infections of S. aureus are becoming difficult to treat, but developing new drugs is a challenge. Repurposing them may be easier. This study looks at the possibility of using hydralazine, a type of medicine used to treat high blood pressure, against S. aureus. The authors found that hydralazine can kill S. aureus and can be used with other antibiotics, including oxacillin and vancomycin. Hydralazine interferes with important processes for the multiplication and survival of this bacterium. These results are preliminary but encouraging. Further studies are needed to confirm the use of hydralazine as a new treatment for S. aureus infections.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Staphylococcus aureus , Methicillin , Methicillin Resistance , Molecular Docking Simulation , Anti-Bacterial Agents/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Microbial Sensitivity Tests
4.
Toxicon ; 238: 107591, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38160738

ABSTRACT

Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G2/M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 µM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells.


Subject(s)
Antineoplastic Agents , Bufanolides , Leukemia , Humans , Leukocytes, Mononuclear , Bromodeoxyuridine/pharmacology , DNA Damage , Antineoplastic Agents/pharmacology , Bufanolides/chemistry , HL-60 Cells , Apoptosis , DNA/pharmacology , Doxorubicin/pharmacology
5.
J Med Microbiol ; 72(9)2023 Sep.
Article in English | MEDLINE | ID: mdl-37707372

ABSTRACT

Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents.Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress.Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis.Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity.Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml-1, with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects.Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Oxacillin , Oxacillin/pharmacology , Vitamin K 3/pharmacology , Methicillin , Staphylococcus aureus , Reactive Oxygen Species , Anti-Bacterial Agents/pharmacology , Biofilms
6.
Future Microbiol ; 18: 1025-1039, 2023 11.
Article in English | MEDLINE | ID: mdl-37540066

ABSTRACT

Aim: Our study evaluated the activity of sertraline (SER) alone and associated with antifungal drugs in planktonic Candida spp. strains, and investigated its mechanism of action. Materials & methods: Broth microdilution method and minimum fungicidal concentration/MIC ratio were used to assess SER anticandidal activity, and the interaction with antifungals was determined by fractional inhibitory concentration index. The mechanism of action was investigated by flow cytometry and in silico tests. Results: SER inhibited Candida spp. strains at low concentrations by the fungicidal effect and showed no loss of effectiveness when combined. Its action seemed to be related to the membrane and cell wall biosynthesis inhibition. Conclusion: SER has activity against Candida spp. isolated and associated with antifungals, and acts by causing cell wall and membrane damage.


Subject(s)
Antifungal Agents , Candida , Antifungal Agents/pharmacology , Sertraline/pharmacology , Cell Wall , Microbial Sensitivity Tests
7.
Future Microbiol ; 18: 661-672, 2023 07.
Article in English | MEDLINE | ID: mdl-37540106

ABSTRACT

Objective: To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against Candida spp. and the action mechanism. Methods: We used broth microdilution assays to determine the MIC, checkerboard assays to investigate synergism, and flow cytometry and molecular docking tests to ascertain action mechanism. Results: Hydralazine alone had antifungal activity in the range of 16-128 µg/ml and synergistic effect with itraconazole versus 100% of the fungal isolates, while there was synergy with fluconazole against 11.11% of the isolates. There was molecular interaction with the receptors exo-B(1,3)-glucanase and CYP51, causing reduced cell viability and DNA damage. Conclusion: Hydralazine is synergistic with itraconazole and triggers cell death of Candida spp. at low concentrations, demonstrating antifungal potential.


Subject(s)
Antifungal Agents , Triazoles , Antifungal Agents/pharmacology , Triazoles/pharmacology , Candida , Itraconazole/pharmacology , Plankton , Molecular Docking Simulation , Fluconazole/pharmacology , Hydralazine/pharmacology , Microbial Sensitivity Tests , Drug Resistance, Fungal
8.
Future Microbiol ; 18: 649-660, 2023 07.
Article in English | MEDLINE | ID: mdl-37522164

ABSTRACT

Aim: To evaluate the antifungal activity of cisatracurium against Candida spp. resistant to fluconazole strains in planktonic and biofilm forms, in addition to determining its mechanism of action. Materials & methods: Antifungal activity and pharmacological interactions were determined using broth microdilution methods and the mechanism of action was evaluated by flow cytometry and molecular docking. Results: Cisatracurium presented antifungal activity against Candida spp. planktonic cells due to alterations of mitochondrial transmembrane potential leading to cellular apoptosis in addition to interacting with important targets related to cellular respiration, membrane and cell wall evidenced by molecular docking. Furthermore, the drug both prevented biofilm formation and impaired mature biofilms. Conclusion: Cisatracurium exhibits potential antifungal activity against Candida spp.


Subject(s)
Antifungal Agents , Fluconazole , Antifungal Agents/pharmacology , Fluconazole/pharmacology , Candida , Molecular Docking Simulation , Biofilms , Microbial Sensitivity Tests , Drug Resistance, Fungal
9.
Future Microbiol ; 18: 505-519, 2023 05.
Article in English | MEDLINE | ID: mdl-37204289

ABSTRACT

Aim: This study was designed to evaluate the in vitro antimicrobial activity of amlodipine against Staphylococcus aureus strains. Materials & methods: The antimicrobial activity of amlodipine was evaluated by the broth microdilution method and its interaction with oxacillin was evaluated by checkerboard assay. The possible mechanism of action was evaluated by flow cytometry and molecular docking techniques. Results: Amlodipine showed activity against S. aureus between 64 and 128 µg/ml, in addition to showing synergism in approximately 58% of the strains used. Amlodipine also showed good activity against forming and mature biofilms. The possible mechanism of action may be attributed to its ability to lead to cell death. Conclusion: Amlodipine has antibacterial activity against S. aureus.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Oxacillin/pharmacology , Staphylococcus aureus , Amlodipine/pharmacology , Molecular Docking Simulation , Drug Synergism , Anti-Bacterial Agents/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Microbial Sensitivity Tests
10.
Future Microbiol ; 18: 415-426, 2023 May.
Article in English | MEDLINE | ID: mdl-37213136

ABSTRACT

Aim: To evaluate the antibacterial activity of paroxetine alone and associated with oxacillin against isolates of methicillin-sensitive and -resistant Staphylococcus aureus. Materials & methods: The broth microdilution and checkerboard techniques were used, with investigation of possible mechanisms of action through flow cytometry, fluorescence microscopy and molecular docking, in addition to scanning electron microscopy for morphological analysis. Results: Paroxetine showed a MIC of 64 µg/ml and bactericidal activity, mostly additive interactions in combination with oxacillin, evidence of action on genetic material and membrane, morphological changes in microbial cells and influence on virulence factors. Conclusion: Paroxetine has antibacterial potential from the perspective of drug repositioning.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Staphylococcus aureus , Paroxetine/pharmacology , Molecular Docking Simulation , Anti-Bacterial Agents/pharmacology , Oxacillin/pharmacology , Staphylococcal Infections/drug therapy , Microbial Sensitivity Tests
11.
J Mol Model ; 29(5): 165, 2023 Apr 29.
Article in English | MEDLINE | ID: mdl-37117952

ABSTRACT

Chagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi, transmitted by the barber insect. Currently, there are approximately 7 million infected people in the world, and it is estimated that 70 million people could contract this disease. The anacardic acid (AA) showed effectiveness in in silico and in vitro tests. The antichagasic potential of five sulfonamide molecules, derived from anacardic acid, was evaluated from a molecular approach based on the density functional theory (DFT), molecular dynamics (MD), and molecular docking (docking) calculations. Methyl 2-methoxy-6- (8- (methylsulfonamide) octyl) benzoate (SA1); 2-methoxy-6- (8- (phenylsulfonamide) octyl) benzoate (SA2); methyl 2-methoxy-6- (8- (2methylphenyl sulfonamide) octyl) benzoate (SA3); methyl 2-methoxy-6- (8-(methylphenylsulfonamide)octyl)benzoate (SA4); methyl2-(8-(2,5-dimethylphenylsulfonamide)octyl)-6-methoxybenzoate (SA5) were the investigated molecules. The DFT calculations were performed using the B3LYP/6-311+G (d, p) level of theory. The global and local reactivity data showed that SA1 shows the highest molecular reactivity, while SA2 is the most stable derivative. In addition, the structures of investigated molecules were confirmed by the linear correlations higher than 0.98 displayed between the experimental and calculated spectroscopic data (IR and NMR). Molecular docking of the molecules showed a greater prominence for the SA1, SA2, and SA4 molecules in the results of distances of ligand-cruzain. In molecular dynamics, SA2 obtained better stability due to greater interactions with important amino acids of cruzain.


Subject(s)
Anacardic Acids , Molecular Dynamics Simulation , Humans , Molecular Docking Simulation , Density Functional Theory , Anacardic Acids/pharmacology , Magnetic Resonance Spectroscopy , Sulfonamides
12.
J Med Microbiol ; 72(2)2023 Feb.
Article in English | MEDLINE | ID: mdl-36762524

ABSTRACT

Candida spp. infections are a serious health problem, especially in patients with risk factors. The acquisition of resistance, often associated with biofilm production, makes treatment more difficult due to the reduced effectiveness of available antifungals. Drug repurposing is a good alternative for the treatment of infections by Candida spp. biofilms. The present study evaluated the in vitro antibiofilm activity of sertraline in reducing the cell viability of forming and matured biofilms, in addition to elucidating whether effective concentrations are safe. Sertraline reduced biofilm cell viability by more than 80 % for all Candida species tested, acting at low and safe concentrations, both on mature biofilm and in preventing its formation, even the one with highest virulence. Its preventive mechanism seemed to be related to binding with ALS3. These data indicate that sertraline is a promising drug with anticandidal biofilm potential in safe doses. However, further studies are needed to elucidate the antibiofilm mechanism and possible application of pharmaceutical forms.


Subject(s)
Candida , Candidiasis , Humans , Sertraline/pharmacology , Sertraline/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Biofilms , Microbial Sensitivity Tests , Candida albicans
13.
Rev. Bras. Saúde Mater. Infant. (Online) ; 23: e20220131, 2023. tab, graf
Article in English | LILACS | ID: biblio-1431252

ABSTRACT

Abstract Objectives: this review aimed to evaluate the adequacy of school menus regarding the nutritional requirements of the Programa Nacional de Alimentação Escolar (PNAE) in Brazilian public schools regarding the presence of macronutrients and micronutrients and allocation of resources to purchase products from family farming. Methods: a systematic literature review was carried out using the SciELO, Bireme and Lilacs databases to select the articles. The inclusion criteria were articles that presented data on the adequacy of energy, macronutrients, micronutrients, and purchases of products from family farming during the PNAE regiment, as well as quantitative, cross-sectional, and descriptive studies carried out in the Brazilian territory. Review, editorials, letters, case studies, duplicates and those that did not assess the requirements of the PNAE were excluded. Results: at the end, 12 studies were included that showed overestimation and underestimation of nutritional adequacy in the school environment. In relation to purchases of inputs from family farming, it was observed that most of the Brazilian municipalities evaluated fulfilled the requirements for the allocation of resources. Conclusion: school menus need more supervision so that they meet the adjustments proposed by the PNAE. In addition, it is essential to promote a healthy diet that contains all the nutrients necessary to provide nutritional support for child growth and development.


Resumo Objetivo: avaliar a adequação dos cardápios escolares quanto às exigências nutricionais do Programa Nacional de Alimentação Escolar (PNAE) em escolas públicas brasileiras considerando quanto a adequação de macronutrientes e micronutrientes e destinação de recursos para compras de produtos advindos da agricultura familiar. Métodos: foi realizada uma revisão sistemática da literatura utilizando as bases de dados SciELO, Bireme e Lilacs para seleção dos artigos. Os critérios de inclusão foram: Artigos que apresentaram dados sobre a adequação de energia, macronutrientes, micronutrientes e compras de produtos oriundos da agricultura familiar durante o regimento do PNAE, assim como estudos quantitativos, transversais e descritivos realizados no território brasileiro. Foram excluídos artigos de revisão, editoriais, cartas ao editor, estudos de caso, artigos em duplicatas e que não avaliaram as exigências do PNAE. Resultados: ao final, foram incluídos12 estudos que apontaram superestimação e subestimação nas adequações nutricionais no ambiente escolar. Em relação às compras de insumo provenientes da agricultura familiar, observou-se que a maioria dos municípios brasileiros avaliados cumpriam as exigências de destinação dos recursos. Conclusões: os cardápios escolares necessitam de maior fiscalização para que atendam as adequações propostas pelo PNAE. Além disso, é primordial promover uma alimentação saudável que contenha todos os nutrientes necessários para fornecer um aporte nutricional para o crescimento e desenvolvimento infantil.


Subject(s)
Humans , Child , School Health Services , School Feeding , Nutrition Programs , Child Nutrition , Recommended Dietary Allowances , National Health Programs , Brazil , Agriculture , Diet, Healthy
14.
J. Health Biol. Sci. (Online) ; 10(1): 1-6, 01/jan./2022. tab, ilus
Article in English | LILACS | ID: biblio-1370924

ABSTRACT

Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.


Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.


Subject(s)
Candida albicans , Silymarin , Proteins , Invasive Fungal Infections
15.
Future Microbiol ; 17: 1363-1379, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36169348

ABSTRACT

Aims: This study aimed to evaluate the antibacterial effect of two new cationic surfactants based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM). Materials & methods: Antibacterial activity, mechanism of action and interactions with Staphylococcus aureus enzymes were measured through microbiological, flow cytometry and molecular docking assays, respectively. Results & conclusion: These compounds showed antibacterial activity in the range of 4.06-16.24 µg/ml against planktonic cells and no activity against mature biofilms, since they caused a loss of membrane integrity and increased DNA damage, as revealed by flow cytometry analysis. In silico assays revealed the existence of molecular bonds such as hydrogen bonds, mainly with DNA. Therefore, these compounds have promising pharmacological activity against MRSA strains.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Staphylococcus aureus , Tryptophan/pharmacology , Microbial Sensitivity Tests , Arginine/pharmacology , Arginine/chemistry , Surface-Active Agents/pharmacology , Molecular Docking Simulation , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms , Phenylalanine/pharmacology
16.
Microb Pathog ; 169: 105664, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35803497

ABSTRACT

A large number of infections are caused by multi-resistant bacteria worldwide, increasing to around 700,000 deaths per year. Because of that, many strategies are being developed to combat the resistance of microorganisms to drugs, and recently, chalcones have been studied for this purpose. Chalcones are known as α, ß-unsaturated ketones, characterized by having the presence of two aromatic rings that are joined by a three-carbon chain. They are a class of compounds considered an exceptional model due to chemical simplicity and a wide variety of biological activities, including anticancer, anti-inflammatory, antioxidants, antimicrobials, anti-tuberculosis, anti-HIV, antimalarial, anti-allergic, antifungal, antibacterial, and antileishmaniasis. The objective of this work was to evaluate the antibacterial and antibiotic modifying activity of chalcone (2E)-1-(4'-aminophenyl)-3-(4-methoxyphenyl)-prop-2-en-1-one against the bacteria Staphylococcus aureus carrying a NorA and MepA efflux pump. The results showed that chalcone showed no toxicity on macrophage cells and was able to synergistically modulate the action of Norfloxacin and Ethidium Bromide against the bacteria Staphylococcus aureus 1199B and K2068, respectively. Furthermore, the theoretical physicochemical and pharmacokinetic properties of chalcone showed that it did not present a severe risk of toxicity such as genetic mutation or cardiotoxicity, constituting an excellent pharmacological active ingredient.


Subject(s)
Chalcone , Chalcones , Staphylococcal Infections , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Chalcone/pharmacology , Chalcones/pharmacology , Humans , Microbial Sensitivity Tests , Multidrug Resistance-Associated Proteins , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/metabolism
17.
J Med Microbiol ; 71(5)2022 May.
Article in English | MEDLINE | ID: mdl-35575783

ABSTRACT

Introduction. Candida spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs.Gap Statement. With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary. This study evaluated the in vitro antifungal activity of chlorogenic acid against fluconazole-resistant strains of Candida spp. Mechanism of action through flow cytometry and in silico analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of Candida albicans associated with the adhesion process and biofilm formation.Results. The chlorogenic acid showed in vitro antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets Thymidylate Kinase, CYP51, 1Yeast Cytochrome BC1 Complex e Exo-B-(1,3)-glucanase demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of C. albicans, important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme.Conclusion. We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti-Candida activity and ability to interact with important drug targets.


Subject(s)
Antifungal Agents , Fluconazole , Antifungal Agents/pharmacology , Apoptosis , Biofilms , Candida , Candida albicans , Chlorogenic Acid/pharmacology , Drug Resistance, Fungal , Fluconazole/pharmacology , Humans , Microbial Sensitivity Tests , Molecular Docking Simulation
18.
Future Microbiol ; 17: 607-620, 2022 05.
Article in English | MEDLINE | ID: mdl-35411812

ABSTRACT

Objective: The present study investigated the antifungal action of dexamethasone disodium phosphate (Dex). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol; M27-A3, checkerboard test and biofilm were evaluated with two isolates of Candida albicans, hyphal production test, molecular docking analysis and flow cytometry analysis. Result: Dex and fluconazole (FLC) together had a synergistic effect. Mature biofilm was reduced when treated with Dex alone or in combination. Dex and FLC promoted a decrease in the production of hyphae and changes in the level of mitochondrial depolarization, increased generation of reactive oxygen species, loss of membrane integrity, increased phosphatidylserine externalization and molecular docking; there was interaction with ALS3 and SAP5 targets. Conclusion: Dex showed antifungal activity against FLC-resistant C. albicans strains.


This study aimed to evaluate the antifungal action of dexamethasone against FLC-resistant C. albicans strains.


Subject(s)
Candida albicans , Fluconazole , Antifungal Agents/pharmacology , Biofilms , Dexamethasone/pharmacology , Drug Resistance, Fungal , Drug Synergism , Fluconazole/pharmacology , Microbial Sensitivity Tests , Molecular Docking Simulation
19.
Can J Microbiol ; 67(12): 885-893, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34314621

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main human pathogens and is responsible for many diseases, ranging from skin infections to more invasive infections. These infections are dangerous and expensive to treat because these strains are resistant to a large number of conventional antibiotics. Thus, the antibacterial effect of ketamine against MRSA strains, its mechanism of action, and in silico interaction with sortase A were evaluated. The antibacterial effect of ketamine was assessed using the broth microdilution method. Subsequently, the mechanism of action was assessed using flow cytometry and molecular docking assays with sortase A. Our results showed that ketamine has a significant antibacterial activity against MRSA strains in the range of 2.49-3.73 mM. Their mechanism of action involves alterations in membrane integrity and DNA damage, reducing cell viability, and inducing apoptosis. In addition, ketamine had an affinity for S. aureus sortase A. These results indicate that this compound can be used as an alternative to develop new strategies to combat infections caused by MRSA.


Subject(s)
Ketamine , Methicillin-Resistant Staphylococcus aureus , Aminoacyltransferases , Anti-Bacterial Agents/pharmacology , Bacterial Proteins , Cysteine Endopeptidases , Humans , Ketamine/pharmacology , Microbial Sensitivity Tests , Molecular Docking Simulation , Staphylococcus aureus
20.
Microb Pathog ; 155: 104892, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33894289

ABSTRACT

Staphylococcus aureus is a commensal bacterium and opportunistic human pathogen that can cause a wide variety of clinical infections. It is recognized for its ability to acquire antimicrobial resistance, so methicillin-resistant Staphylococcus aureus (MRSA) infections are a global healthcare challenge. Therefore, the development of new therapeutic options and alternative therapies for treatment is necessary. Curcumin, a polyphenolic substance found in the rhizome of turmeric longa L, has been shown to have several therapeutic properties, including antimicrobial activity. The objective of the study was to evaluate the in vitro antibacterial activity of curcumin alone and associated with oxacillin against MRSA strains, to analyze the mechanism of cell death involved in the isolated action of curcumin by means of flow cytometry and molecular docking, and to verify its superbiofilm action. Curcumin showed antibacterial activity in the range of 125-500 µg/mL against the tested strains, since it caused an increase in membrane permeability and DNA fragmentation, as revealed by flow cytometry analysis. Moreover, it was possible to observe interactions of curcumin with wild-type S. aureus DHFR, S. aureus gyrase and S. aureus gyrase complex with DNA, DNA (5'-D(*CP*GP*AP*TP*GP*CP*G)-3') and Acyl-PBP2a from MRSA by molecular docking. Curcumin also had a synergistic and additive effect when associated with oxacillin, and significantly reduced the cell viability of the analyzed biofilms. Thus, curcumin is a possible candidate for pharmaceutical formulation development for the treatment of MRSA infections.


Subject(s)
Curcumin , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Biofilms , Curcumin/pharmacology , Humans , Microbial Sensitivity Tests , Molecular Docking Simulation , Plankton , Staphylococcus aureus
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