<i>In Vitro</i> and <i>In Vivo</i> Antiamebic Activity of Iron-Targeting Polypyridine Compounds against Enteric Protozoan Parasite <i>Entamoeba histolytica</i>
<i>In Vitro</i> and <i>In Vivo</i> Antiamebic Activity of Iron-Targeting Polypyridine Compounds against Enteric Protozoan Parasite <i>Entamoeba histolytica</i>
复制标题
铁靶向聚吡啶化合物对肠道原生动物寄生虫<i>溶组织内阿米巴</i>的<i>体外</i>和<i>体内</i>抗阿米巴活性
DOI：
10.1021/acsinfecdis.1c00418
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发表时间：
2022
影响因子：
5.3
通讯作者：
Saito-Nakano Yumiko
中科院分区：
文献类型：
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作者：
Wada Akira;Umeki Yuko;Annoura Takeshi;Saito-Nakano Yumiko
阿米巴病是由溶组织内阿米巴（Entamoeba histolytica）寄生的传染性原生动物引起的，它引起结肠炎和肝脓肿，在发展中国家是一种流行病。目的：开发针对大肠杆菌增殖所需铁源的药物发现策略. histolytica，一个由具有金属结合亲和力的低分子量化合物组成的未开发的化学组。电化学中性多吡啶化合物PHN-R2，表现出特异的Fe（II）结合亲和力和对E的生长抑制能力。组织溶解性。此外，PHN-R2的铁依赖性IC 50值及其铁络合物的光谱分析数据阐明了其抗阿米巴活性与铁靶向特异性之间的关系。PHN-H_2对E.用溶组织杆菌感染的仓鼠作为阿米巴病的动物模型，显示出显著的治疗效果，可完全治愈肝脓肿，且无严重副作用。解读铁靶向化合物在体外和体内的抗阿米巴活性为开发下一代抗阿米巴病药物提供了有价值的见解。
The infectious protozoan parasiteEntamoeba histolyticais responsible for amebiasis causing colitis and liver abscesses, which is an epidemic in developing countries. To develop a drug discovery strategy targeting the iron source required for the proliferation ofE. histolytica, an untapped chemical group consisting of low-molecular-weight compounds with metal-binding affinity was investigated. Electrochemically neutral polypyridine compounds, PHN-R2, that showed specific Fe(II)-binding affinity and growth inhibitory ability againstE. histolyticawere identified. Furthermore, the iron-dependent IC50values of PHN-R2and the spectrometric analytical data of their iron complexes clarified the relationship between the antiamebic activity and the iron-targeting specificity. Notably, when PHN-H2was administrated toE. histolytica-infected hamsters as an animal model of amebiasis, it exhibited a prominent therapeutic efficacy to completely cure liver abscesses without serious side effects. Deciphering the antiamebic activity of iron-targeting compoundsin vitroandin vivoprovides valuable insights into the development of a next-generation drug against amebiasis.