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1.
Future Microbiol ; 18: 1025-1039, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37540066

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 Microbiana
2.
Future Microbiol ; 18: 661-672, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37540106

RESUMO

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 Fúngica
3.
Future Microbiol ; 18: 649-660, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37522164

RESUMO

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.


Assuntos
Antifúngicos , Fluconazol , Antifúngicos/farmacologia , Fluconazol/farmacologia , Candida , Simulação de Acoplamento Molecular , Biofilmes , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica
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