Centre for Advanced Materials and Technologies CEZAMAT, Warsaw University of Technology, Poleczki 19, 02-822 Warsaw, Poland.
Department of Virology, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
Molecules. 2021 Sep 8;26(18):5463. doi: 10.3390/molecules26185463.
Our study aimed to characterise the action mode of -phenacyldibromobenzimidazoles against and . Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure-activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against vs. 4,6-dibromobenzimidazole analogues (- and ). The substitution of chlorine atoms to the benzene ring of the -phenacyl substituent extended the anti- action ( with 2,4-Cl or with 3,4-Cl). The excellent results for -phenacyldibromobenzimidazole against the reference and clinical isolate showed IC = 8 µg/mL and %I = 100 ± 3, respectively. Compound was fungicidal against the isolate. Compound at 160-4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of , in accordance with the patterns observed for the following substrates: 4-nitrophenyl--acetyl-β-d-glucosaminide and 4-nitrophenyl-β-d-,',″-triacetylchitothiose. Derivative at 16 µg/mL: (1) it affected cell wall by inducing β-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the biofilm-treated. Compound exerted -dependent inhibition of virulence factors.
我们的研究旨在描述 -phenacyldibromobenzimidazoles 对 和 的作用模式。首先，我们根据构效关系选择了非细胞毒性的最活性苯并咪唑，结果表明 5,6-二溴苯并咪唑衍生物组对 比对 4,6-二溴苯并咪唑类似物（-和-）的活性较低。-phenacyl 取代基苯环上氯原子的取代扩展了抗作用（带有 2,4-Cl 或 带有 3,4-Cl）。-phenacyldibromobenzimidazole 对 参考和临床分离株的出色结果显示 IC = 8 µg/mL 和 %I = 100 ± 3。化合物 对 分离株具有杀菌作用。化合物 在 160-4 µg/mL 浓度下导致真菌细胞膜不可逆损伤和意外细胞死亡（ACD）。我们报道了 ，符合以下底物观察到的模式：4-硝基苯基--乙酰基-β-d-葡糖胺和 4-硝基苯基-β-d-，′′-三乙酰基壳三糖。衍生物 在 16 µg/mL 时：（1）它通过诱导β-d-葡聚糖酶来影响细胞壁，（2）它导致形态扭曲，（3）在处理的 生物膜中产生渗透不稳定。化合物 对毒力因子表现出 -依赖性抑制作用。
