Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN, 47907, USA.
Bindley Bioscience Center, Purdue University, 1201 W State St., West Lafayette, IN, 47907, USA.
Sci Rep. 2019 Dec 12;9(1):18941. doi: 10.1038/s41598-019-55379-1.
Candida species are a leading source of healthcare infections globally. The limited number of antifungal drugs combined with the isolation of Candida species, namely C. albicans and C. auris, exhibiting resistance to current antifungals necessitates the development of new therapeutics. The present study tested 85 synthetic phenylthiazole small molecules for antifungal activity against drug-resistant C. albicans. Compound 1 emerged as the most potent molecule, inhibiting growth of C. albicans and C. auris strains at concentrations ranging from 0.25-2 µg/mL. Additionally, compound 1 inhibited growth of other clinically-relevant yeast (Cryptococcus) and molds (Aspergillus) at a concentration as low as 0.50 µg/mL. Compound 1 exhibited rapid fungicidal activity, reducing the burden of C. albicans and C. auris below the limit of detection within 30 minutes. Compound 1 exhibited potent antibiofilm activity, similar to amphotericin B, reducing the metabolic activity of adherent C. albicans and C. auris biofilms by more than 66% and 50%, respectively. Furthermore, compound 1 prolonged survival of Caenorhabditis elegans infected with strains of C. albicans and C. auris, relative to the untreated control. The present study highlights phenylthiazole small molecules, such as compound 1, warrant further investigation as novel antifungal agents for drug-resistant Candida infections.
念珠菌属物种是全球医疗保健感染的主要来源。抗真菌药物数量有限，加上念珠菌属物种（即白色念珠菌和耳念珠菌）的分离，这些物种对现有抗真菌药物表现出耐药性，这就需要开发新的治疗方法。本研究测试了 85 种合成苯并噻唑小分子对耐药性白色念珠菌的抗真菌活性。化合物 1 是最有效的分子，在 0.25-2μg/ml 的浓度范围内抑制白色念珠菌和耳念珠菌菌株的生长。此外，化合物 1 在低至 0.50μg/ml 的浓度下即可抑制其他临床相关酵母（隐球菌）和霉菌（曲霉）的生长。化合物 1 表现出快速杀菌活性，在 30 分钟内将白色念珠菌和耳念珠菌的负担减少到检测限以下。化合物 1 表现出很强的抗生物膜活性，与两性霉素 B 相似，分别使粘附的白色念珠菌和耳念珠菌生物膜的代谢活性降低 66%和 50%以上。此外，与未处理的对照组相比，化合物 1 延长了感染白色念珠菌和耳念珠菌菌株的秀丽隐杆线虫的存活时间。本研究强调了苯并噻唑小分子，如化合物 1，值得进一步研究作为治疗耐药性念珠菌感染的新型抗真菌药物。
