Anti-Acanthamoeba metallopharmaceuticals: Amoebicidal activity and synergistic effect of copper(II) coordination compound

IF 4.1 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biometals Pub Date : 2024-04-22 DOI:10.1007/s10534-024-00602-4

Jaqueline da Silveira, Ana Paula Cardoso, Christiane Fernandes, Adolfo Horn Junior, Gabriella da Rosa Monte Machado, Karin Silva Caumo

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Abstract

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 (IC₅₀) 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.

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抗阿卡他米巴金属药物：铜（II）配位化合物的阿米巴杀虫活性和协同效应。

阿卡阿米巴原虫是一种与阿米巴角膜炎有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。其治疗方案治愈率低、毒性大，且需要联合用药。过渡金属化合物具有良好的抗原虫效果。本研究评估了铜(II)配位化合物与洗必泰联合使用的杀阿米巴活性以及局部眼部应用的细胞毒性。研究筛选了这些铜（II）配位化合物对蓖麻棘阿卡他米巴滋养体（ATCC 50492）的杀阿米巴活性。还对兔角膜细胞系（ATCC-CCL 60）进行了细胞毒性测试。这些化合物显示出很高的杀阿米巴潜力，对滋养体活力的抑制率超过 80%。Cp12 和 Cp13 复合物的最小抑制杀阿米巴浓度（MIAC）为 200 µM，平均抑制浓度（IC50）低于 10 µM。在最长的培养期内，Cp12 对包囊的存活率降低了 48%。观察到 Cp12 与洗必泰的协同作用。这些化合物对兔角膜细胞的作用具有剂量依赖性。化合物 Cp12 未来有可能应用于开发针对阿卡阿米巴角膜炎的眼科配方，其在多用途溶液中的应用也值得关注。

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来源期刊

Biometals 生物-生化与分子生物学

CiteScore

5.90

自引率

8.60%

发文量

111

审稿时长

3 months

期刊介绍： BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of: - metal ions - metal chelates, - siderophores, - metal-containing proteins - biominerals in all biosystems. - BioMetals rapidly publishes original articles and reviews. BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.