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

    Francisca BSA do Nascimento

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Lívia GA Valente Sá

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    Christus University Center (UNICHRISTUS), Fortaleza, Ceará, 60190-180, Brazil

    ,
    João B de Andrade Neto

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    Christus University Center (UNICHRISTUS), Fortaleza, Ceará, 60190-180, Brazil

    ,
    Letícia S Sampaio

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Helaine A Queiroz

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Lisandra J Silva

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Vitória PF Cabral

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Daniel S Rodrigues

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Sidsayde C Pereira

    Hospital Dr. Carlos Alberto Studart, Fortaleza, Ceará, 60840-285, Brazil

    ,
    Bruno C Cavalcanti

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    Department of Physiology & Pharmacology, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Jacilene Silva

    Department of Chemistry, Group of Theoretical Chemistry & Electrochemistry (GQTE), State University of Ceará, Limoeiro do Norte, Ceará, 62930-000, Brazil

    ,
    Emmanuel S Marinho

    Department of Chemistry, Group of Theoretical Chemistry & Electrochemistry (GQTE), State University of Ceará, Limoeiro do Norte, Ceará, 62930-000, Brazil

    ,
    Helcio S Santos

    Department of Chemistry, Group of Theoretical Chemistry & Electrochemistry (GQTE), State University of Ceará, Limoeiro do Norte, Ceará, 62930-000, Brazil

    ,
    Manoel O Moraes

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    Department of Physiology & Pharmacology, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    ,
    Hélio V Nobre Júnior

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    &
    Cecília R Silva

    *Author for correspondence: Tel.: +55 853 265 8152;

    E-mail Address: cecilia@ufc.br

    School of Pharmacy, Laboratory of Bioprospection of Antimicrobial Molecules (LABIMAN), Federal University of Ceará, Fortaleza, Ceará, 60430-160, Brazil

    Drug Research & Development Center, Federal University of Ceará, Fortaleza, Ceará, 60430-275, Brazil

    Published Online:https://doi.org/10.2217/fmb-2023-0012

    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.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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