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. 2023 Jul:18:661-672.
doi: 10.2217/fmb-2023-0012. Epub 2023 Aug 4.

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

Francisca Bsa do Nascimento  1   2 , Lívia Ga Valente Sá  1   2   3 , João B de Andrade Neto  1   2   3 , Letícia S Sampaio  1   2 , Helaine A Queiroz  1   2 , Lisandra J Silva  1   2 , Vitória Pf Cabral  1   2 , Daniel S Rodrigues  1   2 , Sidsayde C Pereira  4 , Bruno C Cavalcanti  2   5 , Jacilene Silva  6 , Emmanuel S Marinho  6 , Helcio S Santos  6 , Manoel O Moraes  2   5 , Hélio V Nobre Júnior  1   2 , Cecília R Silva  1   2
Affiliations

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

Francisca Bsa do Nascimento et al. Future Microbiol. 2023 Jul.

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.

Keywords: Candida spp.; apoptosis; hydralazine hydrochloride; molecular docking; triazoles.

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