Synergistic Effect of Hydralazine Associated with Triazoles on Candida spp. in Planktonic Cells

Abstract

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.

Tweetable abstract

We evaluated the effect of hydralazine on Candida spp. and observed its fungicidal effect as a consequence of the damage to the fungal DNA, as well as the enhanced effects of association with itraconazole.

Keywords::

• apoptosis
• Candida spp.
• hydralazine hydrochloride
• molecular docking
• triazoles

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fmb-2023-0012

Author contributions

FBSA do Nascimento: conceptualization, investigation, writing (original draft); LGA Valente Sá: writing (review and editing), analysis; JB de Andrade Neto: validation; LS Sampaio: methodology; HA Queiroz: investigation; LJ da Silva: investigation; VPF Cabral: writing (review and editing); DS Rodrigues: investigation; SC Pereira: resource acquisition; BC Cavalcanti: investigation, methodology; J Silva: methodology; ES Marinho: investigation, methodology; HS dos Santos: investigation, methodology; MO Moraes: conceptualization; HV Nobre Júnior: supervision; CR da Silva: project administration. All authors reviewed the manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.