RESUMEN
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.
Asunto(s)
Antifúngicos , Candida , Antifúngicos/farmacología , Sertralina/farmacología , Pared Celular , Pruebas de Sensibilidad MicrobianaRESUMEN
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.
Asunto(s)
Antifúngicos , Fluconazol , Antifúngicos/farmacología , Fluconazol/farmacología , Candida , Simulación del Acoplamiento Molecular , Biopelículas , Pruebas de Sensibilidad Microbiana , Farmacorresistencia FúngicaRESUMEN
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.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Paroxetina/farmacología , Simulación del Acoplamiento Molecular , Antibacterianos/farmacología , Oxacilina/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
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.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Triptófano/farmacología , Pruebas de Sensibilidad Microbiana , Arginina/farmacología , Arginina/química , Tensoactivos/farmacología , Simulación del Acoplamiento Molecular , Infecciones Estafilocócicas/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas , Fenilalanina/farmacologíaRESUMEN
Aims: To evaluate the antifungal effect of dobutamine against Candida glabrata as well as its synergism with azoles and its action on biofilm. Methods: The M27-A3 protocol and flow cytometry were used for elucidation of the possible mechanism of action. Results: The tested isolates presented MICs ranging from 2 to 32 µg/ml for dobutamine, with fungistatic effect. A total of 82% of the strains showed synergism with fluconazole, with 90% showing synergism with itraconazole. The effect on biofilm formation was nonsignificant. Cytometry tests showed that dobutamine induced mitochondrial depolarization. Conclusion: Dobutamine has an antifungal effect on strains of C. glabrata and synergistic activity with azoles. This effect is probably mediated by increased oxidative damage to the membrane.
Asunto(s)
Azoles , Candida glabrata , Antifúngicos/farmacología , Azoles/farmacología , Dobutamina/farmacología , Farmacorresistencia Fúngica , Fluconazol/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
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.