RESUMO
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.
Assuntos
Antifúngicos , Candida , Antifúngicos/farmacologia , Sertralina/farmacologia , Parede Celular , Testes de Sensibilidade MicrobianaRESUMO
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.
Assuntos
Antifúngicos , Triazóis , Antifúngicos/farmacologia , Triazóis/farmacologia , Candida , Itraconazol/farmacologia , Plâncton , Simulação de Acoplamento Molecular , Fluconazol/farmacologia , Hidralazina/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência FúngicaRESUMO
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.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Paroxetina/farmacologia , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Oxacilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
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.
Assuntos
Candida albicans , Fluconazol , Antifúngicos/farmacologia , Biofilmes , Dexametasona/farmacologia , Farmacorresistência Fúngica , Sinergismo Farmacológico , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento MolecularRESUMO
Aim: To evaluate the antifungal activity of gallic acid (GA) against the strains of Candida spp. resistant to fluconazole and to determine its mechanism of action. Materials & methods: Antifungal activity was evaluated using the broth microdilution and flow cytometry techniques. Results: GA presented minimum inhibitory concentrations ranging from 16 to 72 µg/ml, causing alterations of the membrane integrity and mitochondrial transmembrane potential, production of reactive oxygen species and externalization of phosphatidylserine. Conclusion: GA has potential antifungal activity against Candida spp.
Assuntos
Antifúngicos , Candida albicans , Antifúngicos/farmacologia , Apoptose , Morte Celular , Farmacorresistência Fúngica , Fluconazol/farmacologia , Ácido Gálico/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Aim: To evaluate the activity of diclofenac sodium and synergism with oxacillin against clinical strains of SARM in plactonic cells, antibiofilm and biofilm. Materials & methods: Synergism activity was assessed using the fractional inhibitory concentration index and its possible mechanism of action by flow cytometry. Results: The synergistic activity of diclofenac sodium with oxacillin was observed against plactonic cells, antibiofilm and in biofilm formed from clinical methicillin-resistant Staphylococcus aureus strains. Conclusion: This combination caused damage to the integrity of the membrane and ruptures in the DNA of the cells, leading to apoptosis.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Diclofenaco/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxacilina/farmacologia , Biofilmes/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade MicrobianaRESUMO
Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125-250 µg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 µg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase/microbiologia , Midazolam/farmacologia , Biofilmes/efeitos dos fármacos , Candida/genética , Candida/crescimento & desenvolvimento , Candida/fisiologia , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Fúngica , Fluconazol/farmacologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Aim: The purpose of this study was to assess the antifungal effect of ß-lapachone (ß-lap) on azole-resistant strains of Candida spp. in both planktonic and biofilm form. Materials & methods: The antifungal activity of ß-lap was evaluated by broth microdilution, flow cytometry and the comet assay. The cell viability of the biofilms was assessed using the MTT assay. Results: ß-lap showed antifungal activity against resistant strains of Candida spp. in planktonic form. In addition, ß-lap decreased the viability of mature biofilms and inhibited the formation of biofilms in vitro. Conclusion: ß-lap showed antifungal activity against Candida spp., suggesting that the compound can be utilized as an adjunct agent in the treatment of candidiasis.
Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Farmacorresistência Fúngica , Naftoquinonas/farmacologia , Candida/fisiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Aim: The purpose of this study was to evaluate the antimicrobial activity of the anesthetic etomidate against strains of MRSA and biofilms. Materials & methods: The antibacterial effect of etomidate was assessed by the broth microdilution method. To investigate the probable action mechanism of the compound flow cytometry techniques were used. Results: MRSA strains showed MIC equal to 500 and 1000 µg/ml of etomidate. Four-fifths (80%) of the tested MRSA strains demonstrated synergistic effect with oxacillin. Etomidate also showed activity against MRSA biofilm at concentration of 250 µg/ml. Cytometric analysis revealed that the cells treated with etomidate leading to cell death, probably by apoptosis. Conclusion: Etomidate showed antibacterial activity against MRSA.
Assuntos
Antibacterianos/farmacologia , Etomidato/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Oxacilina/farmacologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologiaRESUMO
Synthetically derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(-)-1], both of which are examples of naturally occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8, and SF-295 tumor cell lines. As a result it was established that compound (+)-1 was particularly active with OVCAR-8 cells being the most sensitive and responding in a dose-dependent manner. A study of cell viability and drug-induced morphological changes revealed the compound causes cell death through a mechanism characteristic of apoptosis. Finally, a computational study of the interactions of compound (+)-1 and (S)-monastrol, an established, synthetically derived, potent, and cell-permeant inhibitor of mitosis, with the kinesin-type protein Eg5 revealed that both bind to this receptor in a similar manner. Significantly, compound (+)-1 binds with greater affinity, an effect attributed to the presence of the associated methoxy groups.