Fungal infections that affect humans and plants have increased significantly in recent decades. However, these pathogens are still neglected when compared to other infectious agents. Due to the high prevalence of these infections, the need for new molecules with antifungal potential is recognized, as pathogenic species are developing resistance to the main drugs available. This work reports the design and synthesis of 1,2,3-triazole derivatives of 8-hydroxyquinoline, as well as the determination of their activities against a panel of fungal species: Candida spp., Trichosporon asahii, Magnusiomyces capitatus, Microsporum spp., Trichophyton spp. and Fusarium spp. The triazoles 5-(4-phenyl-1H-1,2,3-triazol-1-yl)quinolin-8-ol (12) and 5-(4-(cyclohex-1-en-1-yl)-1H-1,2,3-triazol-1-yl)quinolin-8-ol (16) were more promising, presenting minimum inhibitory concentration (MIC) values between 1–16 µg/ml for yeast and 2–4 µg/ml for dermatophytes. However, no relevant anti-Fusarium spp. activity was observed. In the time-kill assays with Microsporum canis, 12 and 16 presented time-dependent fungicide profile at 96 h and 120 h in all evaluated concentrations, respectively. For Candida guilliermondii, 12 was fungicidal at all concentrations at 6 h and 16 exhibited a predominantly fungistatic profile. Both 12 and 16 presented low leukocyte toxicity at 4 µg/ml and the cell viability was close to 100% after the treatment with 12 at all tested concentrations. The sorbitol assay combined with SEM suggest that damages on the fungal cell wall could be involved in the activity of these derivatives. Given the good results obtained with this series, scaffold 4-(cycloalkenyl or phenyl)-5-triazol-8-hydroxyquinoline appears to be a potential pharmacophore for exploration in the development of new antifungal agents.

中文翻译：

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具有前景和选择性抗真菌活性的 8-羟基喹啉 1,2,3-三唑衍生物

近几十年来，影响人类和植物的真菌感染显着增加。然而，与其他传染性病原体相比，这些病原体仍然被忽视。由于这些感染的高发率，人们认识到需要具有抗真菌潜力的新分子，因为病原体正在对可用的主要药物产生抗药性。这项工作报告了 8-羟基喹啉的 1,2,3-三唑衍生物的设计和合成，以及它们对一组真菌物种的活性的测定：念珠菌属。, Trichosporon asahii, Magnusiomyces capitus, Microsporum spp。, 毛癣菌属。和镰刀菌属。三唑类 5-(4-phenyl-1 H-1,2,3-triazol-1-yl)quinolin-8-ol ( 12 ) 和 5-(4-(cyclohex-1-en-1-yl)-1 H -1,2,3-triazol- 1-yl)quinolin-8-ol ( 16 ) 更有希望，其最低抑菌浓度 (MIC) 值介于 1–16  µg /ml 酵母和 2–4  µg /ml 皮肤癣菌之间。然而，没有相关的抗镰刀菌属。观察到活性。在犬小孢子菌的时间杀灭试验中，12和16分别在所有评估浓度下在 96 小时和 120 小时呈现出时间依赖性杀菌剂特征。对于guilliermondii 念珠菌，12在所有浓度下均在 6 小时和16表现出主要的抑真菌特征。12和16在 4 µg /ml 时都表现出低白细胞毒性， 并且在所有测试浓度下用12处理后细胞活力接近 100% 。山梨糖醇测定结合 SEM 表明真菌细胞壁的损伤可能与这些衍生物的活性有关。鉴于该系列获得的良好结果，支架 4-（环烯基或苯基）-5-三唑-8-羟基喹啉似乎是开发新型抗真菌剂的潜在药效团。