Analysis of the anti-Candida activity of tricyclic antidepressants in association with amphotericin B and their antifungal mechanisms.

Autor: de Farias Cabral VP; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., Rodrigues DS; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., do Amaral Valente Sá LG; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil.; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil., Moreira LEA; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., da Silva CR; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., de Andrade Neto JB; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil.; Christus University Center (UNICHRISTUS), Fortaleza, CE, Brazil., da Costa ÉRM; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., Ferreira TL; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., de Oliveira LC; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., de Souza BO; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil., Cavalcanti BC; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., Magalhães IL; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., de Moraes MO; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil., Júnior HVN; School of Pharmacy, Laboratory of Bioprospection in Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, CE, Brazil. label_ufc@yahoo.com.br.; Center of Drug Research and Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil. label_ufc@yahoo.com.br.
Jazyk: angličtina
Zdroj: Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] [Braz J Microbiol] 2024 Aug 29. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1007/s42770-024-01459-y
Abstrakt: Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128 µg/mL, NOR from 8 to 128 µg/mL, and CLO from 8 to 64 µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.
(© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)
Databáze: MEDLINE
Externí odkaz: