Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Unidad de Microanálisis y Métodos Físicos en Química Orgánica (UMYMFOR), C1428EHA, Buenos Aires, Argentina.
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Unidad de Microanálisis y Métodos Físicos en Química Orgánica (UMYMFOR), C1428EHA, Buenos Aires, Argentina.
Eur J Med Chem. 2023 Dec 15;262:115885. doi: 10.1016/j.ejmech.2023.115885. Epub 2023 Oct 16.
The opportunistic apicomplexan parasite Toxoplasma gondii is the etiologic agent for toxoplasmosis, which can infect a widespread range of hosts, particularly humans and warm-blooded animals. The present chemotherapy to treat or prevent toxoplasmosis is deficient and is based on diverse drugs such as atovaquone, trimethoprim, spiramycine, which are effective in acute toxoplasmosis. Therefore, a safe chemotherapy is required for toxoplasmosis considering that its responsible agent, T. gondii, provokes severe illness and death in pregnant women and immunodeficient patients. A certain disadvantage of the available treatments is the lack of effectiveness against the tissue cyst of the parasite. A safe chemotherapy to combat toxoplasmosis should be based on the metabolic differences between the parasite and the mammalian host. This article covers different relevant molecular targets to combat this disease including the isoprenoid pathway (farnesyl diphosphate synthase, squalene synthase), dihydrofolate reductase, calcium-dependent protein kinases, histone deacetylase, mitochondrial electron transport chain, etc.
机会致病顶复门原虫刚地弓形虫是弓形体病的病原体,可感染广泛的宿主,特别是人类和温血动物。目前用于治疗或预防弓形体病的化疗方法存在缺陷,主要基于多种药物,如阿托伐醌、三甲氧苄氨嘧啶、螺旋霉素,这些药物对急性弓形体病有效。因此,鉴于其病原体刚地弓形虫会导致孕妇和免疫功能低下患者重病和死亡,需要一种安全的化疗方法来治疗弓形体病。现有治疗方法的一个缺点是对寄生虫的组织包囊无效。一种安全的抗弓形体病化疗方法应该基于寄生虫和哺乳动物宿主之间的代谢差异。本文涵盖了不同的相关分子靶点来对抗这种疾病,包括异戊烯途径(法呢基二磷酸合酶、鲨烯合酶)、二氢叶酸还原酶、钙依赖性蛋白激酶、组蛋白去乙酰化酶、线粒体电子传递链等。