A Novel Multistage Antiplasmodial Inhibitor Targeting Plasmodium Falciparum Histone Deacetylase 1

Overview

Journal Cell Discov

Date 2020 Dec 14

PMID 33311461

Citations 12

Authors

Zhenghui Huang

Ruoxi Li

Tongke Tang

Dazheng Ling

Manjiong Wang

Dandan Xu

Maoxin Sun

Lulu Zheng

Feng Zhu

Hui Min

Rachasak Boonhok

Yan Ding

Yuhao Wen

Yicong Chen

Xiaokang Li

Yuxi Chen

Taiping Liu

Jiping Han

Jun Miao

Qiang Fang

Yaming Cao

Yun Tang

Jie Cui

Wenyue Xu

Liwang Cui

Jin Zhu

Gary Wong

Jian Li

Lubin Jiang

Affiliations

Soon will be listed here.

Abstract

Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites. JX21108 was developed from chemical optimization of quisinostat, a histone deacetylase inhibitor. We identified P. falciparum histone deacetylase 1 (PfHDAC1), an epigenetic regulator essential for parasite growth and invasion, as a molecular target of JX21108. PfHDAC1 knockdown leads to the downregulation of essential parasite genes, which is highly consistent with the transcriptomic changes induced by JX21108 treatment. Collectively, our data support that PfHDAC1 is a potential drug target for overcoming multidrug resistance and that JX21108 treats malaria and blocks parasite transmission simultaneously.

Citing Articles

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