Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Selangor, Malaysia.
Department of Clinical Sciences, College of Medicine, University of Sharjah, University City, Sharjah, United Arab Emirates.
Chemotherapy. 2022;67(3):183-192. doi: 10.1159/000520585. Epub 2021 Nov 1.
Acanthamoeba castellanii is a pathogenic free-living amoeba responsible for blinding keratitis and fatal granulomatous amoebic encephalitis. However, treatments are not standardized but can involve the use of amidines, biguanides, and azoles.
The aim of this study was to synthesize a variety of synthetic tetrazole derivatives and test their activities against A. castellanii.
A series of novel tetrazole compounds were synthesized by one-pot method and characterized by NMR and mass spectroscopy. These compounds were subjected to amoebicidal and cytotoxicity assays against A. castellanii belonging to the T4 genotype and human keratinocyte skin cells, respectively. Additionally, reactive oxygen species determination and electron microscopy studies were carried out. Furthermore, two of the seven compounds were conjugated with silver nanoparticles to study their anti-amoebic potential.
A series of seven tetrazole derivatives were synthesized successfully. The selected tetrazoles showed anti-amoebic activities at 10 μM concentration against A. castellanii in vitro. The compounds tested caused increased reactive oxygen species generation in A. castellanii and morphological damage to amoebal membranes. Moreover, conjugation of silver nanoparticles enhanced anti-amoebic effects of two tetrazoles.
The results showed that azole compounds hold promise in the development of new formulations of anti-Acanthamoebic agents.
棘阿米巴属是一种致病的自由生活阿米巴原虫，可导致致盲性角膜炎和致命性肉芽肿性阿米巴脑炎。然而，目前的治疗方法尚未标准化，但可以使用脒类、双胍类和唑类药物。
本研究旨在合成多种合成的四唑衍生物，并测试其对棘阿米巴属的活性。
通过一锅法合成了一系列新型四唑化合物，并通过 NMR 和质谱进行了表征。将这些化合物分别进行杀阿米巴和细胞毒性测定，以评估其对属于 T4 基因型的棘阿米巴属和人角质形成细胞的活性。此外，还进行了活性氧测定和电子显微镜研究。进一步地，将其中两种化合物与银纳米粒子缀合，以研究其抗阿米巴活性。
成功合成了一系列 7 种四唑衍生物。在所测试的浓度为 10 μM 时，这些四唑化合物对体外培养的棘阿米巴属具有抗阿米巴活性。测试化合物可引起棘阿米巴属中活性氧的生成增加，并导致阿米巴细胞膜形态损伤。此外，银纳米粒子的缀合增强了两种四唑化合物的抗阿米巴活性。
研究结果表明，唑类化合物在开发新的抗棘阿米巴制剂方面具有潜力。
