双膦酸盐抗三种顶复门原虫研究进展

Research progress in bisphosphonates against three apicomplexan protozoa

顶复门原虫可引起严重疾病威胁人类健康,如每年导致近100万人死亡的疟原虫,感染全球约1/3人口的弓形虫以及导致新生儿腹泻的隐孢子虫等。这3种顶复门原虫对全球的生物安全和公共卫生构成巨大隐患,且目前在临床上有效治疗药物有限。双膦酸盐临床上广泛用于治疗骨代谢疾病,但其化合物可有效抑制顶复门原虫生长,作用机制为竞争性抑制寄生虫类异戊二烯分子生物合成的2C-甲基-D-赤藓糖醇-4-磷酸途径(MEP途径)中的法尼基焦磷酸合酶,干扰类异戊二烯化合物的合成而发挥作用。本文综述了双膦酸盐化合物在疟原虫、弓形虫和隐孢子虫方面的相关研究,以期为临床治疗相关疾病提供理论基础。

Apicomplexan protozoa can cause severe disease and threaten human health.These protozoa include Plasmodium,which causes nearly 1 million deaths each year,Toxoplasma,which infects approximately one-third of the world’s population,and Cryptosporidium,which causes neonatal diarrhea.These three apicomplexan protozoa pose a major threat to global biosecurity and public health,and limited effective clinical treatments are currently available.Bisphosphonates have been widely used in the treatment of bone metabolic diseases and have been found to effectively inhibit the growth of apicomplexan protozoa.The mechanism of action involves competitive inhibition of farnesyl pyrophosphate synthase in the MEP pathway for the biosynthesis of isoprenoid molecules in parasites.Farnesyl pyrophosphate synthase functions by interfering with the synthesis of isoprenoid compounds.This article reviews research on bisphosphonate compounds in Plasmodium,Toxoplasma,and Cryptosporidium,to provide a theoretical basis for the clinical treatment of related diseases.