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疟原虫恶性疟原虫寄生虫过表达法呢基二磷酸合酶/香叶基二磷酸合酶对利塞膦酸钠的耐药性增强。

Plasmodium falciparum parasites overexpressing farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase are more resistant to risedronate.

机构信息

Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.

Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP, Brazil.

出版信息

Mem Inst Oswaldo Cruz. 2018;113(10):e180174. doi: 10.1590/0074-02760180174. Epub 2018 Aug 13.

Abstract

Farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains. Risedronate, a bisphosphonate containing nitrogen (N-BP), is a potent inhibitor of blood stage Plasmodium. Here, we show that P. falciparum parasites overexpressing FPPS/GGPPS are more resistant to risedronate, suggesting that this enzyme is an important target, and bisphosphonate analogues can be used as potential antimalarial drugs.

摘要

法呢基二磷酸合酶/香叶基二磷酸合酶(FPPS/GGPPS)是异戊烯链合成的关键酶。利塞膦酸盐,一种含氮的双膦酸盐(N-BP),是血期疟原虫的有效抑制剂。在这里,我们表明过表达 FPPS/GGPPS 的恶性疟原虫寄生虫对利塞膦酸盐更具抗性,表明该酶是一个重要的靶标,并且双膦酸盐类似物可以用作潜在的抗疟药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcae/6086031/aa1d5eff6010/1678-8060-mioc-113-10-e180174-gf1.jpg

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