University of Alcala, Department of Biomedicine and Biotechnology, 28805, Madrid, Spain.
University of Alcala, Department of Organic and Inorganic Chemistry, and Research Institute in Chemistry "Andrés M. del Río" (IQAR), 28805, Madrid, Spain.
Parasitol Res. 2024 Nov 30;123(12):401. doi: 10.1007/s00436-024-08413-9.
Acanthamoeba species are responsible for serious human infections, including Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). These pathogens have a simple life cycle consisting of an infective trophozoite stage and a resistant cyst stage, with cysts posing significant treatment challenges due to their resilience against harsh conditions and chemical agents. Current treatments for AK often involve combining diamines, such as propamidine, and biguanides, such as chlorhexidine (CLX), which exhibit limited efficacy and significant toxicity. Thus, the effect of new therapeutic molecules, such as multifunctional systems (e.g., carbosilane dendritic molecules), should be studied as potential alternatives due to their biocidal properties and lower toxicity. This study evaluates various dendritic compounds against trophozoites and cysts of two Acanthamoeba clinical isolates, both alone and in combination with CLX, and assesses their cytotoxicity on HeLa cells. The results indicated that certain dendritic compounds, especially BDSQ024, were effective against both trophozoites and cysts. Additionally, combinations of dendritic molecules and CLX showed enhanced efficacy in eliminating trophozoites and cysts, suggesting potential for synergistic treatments. The study underscores the promise of dendritic molecules in developing more effective and less toxic therapies for Acanthamoeba infections.
棘阿米巴属物种是导致严重人类感染的原因,包括棘阿米巴角膜炎(AK)和肉芽肿性阿米巴脑炎(GAE)。这些病原体具有简单的生命周期,包括感染性滋养体阶段和具有抗性的囊阶段,由于其对恶劣条件和化学制剂的抵抗力,囊对治疗构成了重大挑战。目前 AK 的治疗方法通常涉及联合使用二甲胺,如丙脒,和双胍,如洗必泰(CLX),这些方法的疗效有限,毒性显著。因此,由于新的治疗分子,如多功能系统(例如,碳硅烷树状分子)具有杀菌特性和较低的毒性,应该研究它们作为潜在替代品的效果。本研究评估了各种树状化合物对两种棘阿米巴临床分离株的滋养体和囊的单独作用以及与 CLX 联合作用的效果,并评估了它们对 HeLa 细胞的细胞毒性。结果表明,某些树状化合物,特别是 BDSQ024,对滋养体和囊均有效。此外,树状分子与 CLX 的组合在消除滋养体和囊方面显示出增强的疗效,表明可能存在协同治疗作用。该研究强调了树状分子在开发针对棘阿米巴感染的更有效和毒性更低的治疗方法方面的潜力。