Treatment of Acanthamoeba keratitis (AK) is difficult because Acanthamoeba cysts are resistant to drugs, and as such, successful treatment requires an effective approach that inhibits cyst formation. Histone deacetylase inhibitors (HDACis) are involved in cell proliferation, differentiation, and apoptotic cell death. In this study, the effects of HDACis such as MPK472 and KSK64 on Acanthamoeba castellanii trophozoites and cysts were observed. MPK472 and KSK64 showed at least 60% amoebicidal activity against Acanthamoeba trophozoites at a concentration of 10 μM upon 8 h of treatment. Neither of the two HDACis affected mature cysts, but significant amoebicidal activities (36.4 and 33.9%) were observed against encysting Acanthamoeba following treatment with 5 and 10 μM HDACis for 24 h. Light microscopy and transmission electron microscopy results confirmed that the encystation of Acanthamoeba was inhibited by the two HDACis. In addition to this, low cytopathic effects on human corneal epithelial (HCE) cells were observed following treatment with MPK472 and KSK64 for 24 h. Our results indicate that the HDACis MPK472 and KSK64 could be used as new candidates for the development of an optimal therapeutic option for AK.

中文翻译：

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组蛋白脱乙酰基酶抑制剂MPK472和KSK64作为棘阿米巴角膜炎的潜在治疗选择。

棘阿米巴角膜炎（AK）的治疗很困难，因为棘阿米巴囊肿对药物有抵抗力，因此，成功的治疗需要抑制囊肿形成的有效方法。组蛋白脱乙酰基酶抑制剂（HDACis）参与细胞增殖，分化和凋亡性细胞死亡。在这项研究中，观察到HDACis，例如MPK472和KSK64对棘阿米巴Castellanii滋养体和囊肿的影响。处理8小时后，MPK472和KSK64在浓度为10μM时，对棘阿米巴滋养体显示出至少60％的杀菌活性。两个HDAC均未影响成熟囊肿，但观察到显着的杀螨活性（36.4％和33.9％）用5和10μMHDAC处理棘阿米巴24小时。光显微镜和透射电子显微镜结果证实的成囊棘阿米巴是由两个HDACis抑制。除此之外，在用MPK472和KSK64处理24小时后，观察到对人角膜上皮（HCE）细胞的细胞病变作用较低。我们的结果表明，HDACis MPK472和KSK64可用作开发AK最佳治疗选择的新候选药物。