Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Laboratório de Investigação Aplicada a Protozoários Emergentes (LADIPE), Florianópolis, Santa Catarina, 88040-970, Brazil.
Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
Biometals. 2024 Oct;37(5):1225-1236. doi: 10.1007/s10534-024-00602-4. Epub 2024 Apr 22.
Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492). The cytotoxicity on rabbit corneal cell line (ATCC-CCL 60) was performed. The compounds showed high amoebicidal potential, with inhibition of trophozoite viability above 80%. The Cp12 and Cp13 compounds showed Minimal Inhibitory Amoebicidal Concentration (MIAC) at 200 µM and mean inhibitory concentration (IC) values lower than 10 µM. Against the cysts, Cp12 showed a reduction in viability (48%) in the longest incubation period. A synergistic effect for Cp12 with chlorhexidine was observed. The compounds have a dose-dependent effect against rabbit corneal cells. Compound Cp12 has potential for future application in developing ophthalmic formulations against Acanthamoeba keratitis and its use in multipurpose solutions is highlighted.
棘阿米巴属已成为一种与阿米巴角膜炎相关的重要临床病原体。它是眼科角膜移植和视力丧失的主要原因之一。治疗方案的治愈率低、毒性高，需要联合用药。过渡金属化合物已显示出有希望的抗原生动物作用。本研究评估了铜（II）配合物与洗必泰联合应用的杀阿米巴活性及其对眼部局部应用的细胞毒性。这些铜（II）配合物针对棘阿米巴属滋养体（ATCC 50492）进行了筛选。对兔角膜细胞系（ATCC-CCL 60）进行了细胞毒性测定。这些化合物表现出很高的杀阿米巴活性，对滋养体活力的抑制作用超过 80%。Cp12 和 Cp13 化合物在 200µM 时表现出最小抑菌杀阿米巴浓度（MIAC），平均抑制浓度（IC）值低于 10µM。对于囊肿，Cp12 在最长孵育期表现出 48%的活力降低。观察到 Cp12 与洗必泰具有协同作用。这些化合物对兔角膜细胞具有剂量依赖性作用。化合物 Cp12 具有开发针对棘阿米巴角膜炎的眼科制剂的潜力，其在多用途溶液中的应用得到了强调。
