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.
Future Microbiol. 2023 Jul;18:661-672. doi: 10.2217/fmb-2023-0012. Epub 2023 Aug 4.
To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against spp. and the action mechanism. 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. 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. Hydralazine is synergistic with itraconazole and triggers cell death of spp. at low concentrations, demonstrating antifungal potential.
为评估盐酸肼屈嗪单独及与唑类药物联合应用对 spp. 的抗真菌活性及作用机制。我们采用肉汤微量稀释法测定 MIC,棋盘试验检测协同作用,流式细胞术和分子对接试验确定作用机制。盐酸肼屈嗪单独使用时对范围在 16-128μg/ml 的真菌具有抗真菌活性,并与伊曲康唑对 100%的真菌分离株具有协同作用,而与氟康唑对 11.11%的分离株具有协同作用。与受体外-β(1,3)-葡聚糖酶和 CYP51 存在分子相互作用,导致细胞活力降低和 DNA 损伤。盐酸肼屈嗪与伊曲康唑具有协同作用,并在低浓度下触发 spp. 的细胞死亡,显示出抗真菌潜力。