Sertraline has fungicidal activity against Candida spp. and acts by inhibiting membrane and cell wall biosynthesis.

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.

Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells.

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.

Antifungal activity of cisatracurium against fluconazole-resistant Candida isolates and its antibiofilm effects.

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.

Activity of amlodipine against Staphylococcus aureus: association with oxacillin and mechanism of action.

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.

Antibacterial activity of paroxetine against Staphylococcus aureus and possible mechanisms of action.

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.

Synergistic activity of dobutamine combined with azoles and its mechanism of action against strains of Candida glabrata.

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.

Gallic acid leads to cell death of Candida albicans by the apoptosis mechanism.

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.