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

被引:3
|
作者
do Nascimento, Francisca B. S. A. [1 ,2 ]
Valente Sa, Livia G. A. [1 ,2 ,4 ]
de Andrade Neto, Joao B. [1 ,2 ,4 ]
Sampaio, Leticia S. [1 ,2 ]
Queiroz, Helaine A. [1 ,2 ]
Silva, Lisandra J. [1 ,2 ]
Cabral, Vitoria P. F. [1 ,2 ]
Rodrigues, Daniel S. [1 ,2 ]
Pereira, Sidsayde C. [5 ]
Cavalcanti, Bruno C. [2 ,3 ]
Silva, Jacilene [6 ]
Marinho, Emmanuel S. [6 ]
Santos, Helcio S. [6 ]
Moraes, Manoel O. [2 ,3 ]
Junior, Helio V. N. [1 ,2 ]
Silva, Cecilia R. [1 ,2 ]
机构
[1] Univ Fed Ceara, Sch Pharm, Lab Bioprospect Antimicrobial Mol LABIMAN, BR-60430160 Fortaleza, CE, Brazil
[2] Univ Fed Ceara, Drug Res & Dev Ctr, BR-60430275 Fortaleza, CE, Brazil
[3] Univ Fed Ceara, Dept Physiol & Pharmacol, BR-60430275 Fortaleza, CE, Brazil
[4] Christus Univ Ctr UNICHRISTUS, BR-60190180 Fortaleza, CE, Brazil
[5] Hosp Dr Carlos Alberto Studart, BR-60840285 Fortaleza, CE, Brazil
[6] Univ Estadual Ceara, Dept Chem, Grp Theoret Chem & Electrochem GQTE, BR-62930000 Limoeiro Norte, CE, Brazil
关键词
apoptosis; Candida spp; hydralazine hydrochloride; molecular docking; triazoles; ANTIHYPERTENSIVE DRUG HYDRALAZINE; ALBICANS; INHIBITION; 14-ALPHA-DEMETHYLASE; PERFORMANCE; RESISTANCE; MECHANISM; DOCKING;
D O I
10.2217/fmb-2023-0012
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 & mu;g/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 abstractWe 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.
引用
收藏
页码:661 / 672
页数:12
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