Acanthamoeba are known to cause a vision threatening eye infection typically due to contact lens wear, and an infection of the central nervous system. The ability of these amoebae to switch phenotypes, from an active trophozoite to a resistant cyst form is not well understood; the cyst stage is often resistant to chemotherapy, which is of concern given the rise of contact lens use and the ineffective disinfectants available, versus the cyst stage. Herein, for the first time, a range of raloxifene sulfonate/sulfamate derivatives which target nucleotide pyrophosphatase/phosphodiesterase enzymes, were assessed using amoebicidal and excystation tests versus the trophozoite and cyst stage of Acanthamoeba. Moreover, the potential for cytopathogenicity inhibition in amoebae was assessed. Each of the derivatives showed considerable anti-amoebic activity as well as the ability to suppress phenotypic switching (except for compound 1a). Selected raloxifene derivatives reduced Acanthamoeba-mediated host cell damage using lactate dehydrogenase assay. These findings suggest that pyrophosphatase/phosphodiesterase enzymes may be valuable targets against Acanthamoeba infections.

已知棘阿米巴会导致威胁视力的眼部感染（通常是由于佩戴隐形眼镜）和中枢神经系统感染。这些变形虫从活跃的滋养体转变为抗性包囊形式的表型的能力尚不清楚。囊肿期通常对化疗有抵抗力，考虑到隐形眼镜使用的增加和可用的消毒剂与囊肿期相比无效，这一点值得关注。在此，首次使用杀阿米巴和去囊试验与棘阿米巴的滋养体和囊肿阶段对一系列靶向核苷酸焦磷酸酶/磷酸二酯酶的雷洛昔芬磺酸盐/氨基磺酸盐衍生物进行了评估。此外，还评估了阿米巴原虫细胞致病性抑制的潜力。每种衍生物都显示出相当大的抗阿米巴活性以及抑制表型转换的能力（化合物1a除外）。使用乳酸脱氢酶测定，选择的雷洛昔芬衍生物减少棘阿米巴介导的宿主细胞损伤。这些发现表明焦磷酸酶/磷酸二酯酶可能是对抗棘阿米巴感染的有价值的靶标。