Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells.
Francisca Bsa do NascimentoLívia Gurgel do Amaral Valente SáJoão Batista de Andrade NetoLetícia Ss MorenoHelaine Almeida QueirozLisandra Juvêncio da SilvaVitória Pessoa de Farias CabralDaniel Sampaio RodriguesSidsayde C PereiraBruno Coêlho CavalcantiJacilene SilvaEmanuelle Machado MarinhoHélcio Silva Dos SantosManoel Odorico DE-MoraesHélio Vitoriano Nobre JúniorCecília Rocha da SilvaPublished in: Future microbiology (2023)
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.
Keyphrases
- candida albicans
- molecular docking
- flow cytometry
- cell death
- dna damage
- biofilm formation
- cell cycle arrest
- induced apoptosis
- high throughput
- molecular dynamics simulations
- genetic diversity
- oxidative stress
- dna repair
- cancer therapy
- single molecule
- staphylococcus aureus
- cell proliferation
- climate change
- signaling pathway
- drug delivery
- human health
- single cell