| Literature DB >> 33311461 |
Zhenghui Huang1, Ruoxi Li2,3, Tongke Tang4,5, Dazheng Ling2,3, Manjiong Wang2,3, Dandan Xu6, Maoxin Sun4,5, Lulu Zheng3, Feng Zhu7, Hui Min7, Rachasak Boonhok7, Yan Ding8, Yuhao Wen4, Yicong Chen4, Xiaokang Li2,3, Yuxi Chen9, Taiping Liu8, Jiping Han4, Jun Miao7, Qiang Fang6, Yaming Cao9, Yun Tang3, Jie Cui4, Wenyue Xu8, Liwang Cui7, Jin Zhu2,3, Gary Wong4, Jian Li10,11, Lubin Jiang12,13.
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.Entities:
Year: 2020 PMID： 33311461 DOI： 10.1038/s41421-020-00215-4
Source DB: PubMed Journal: Cell Discov ISSN： 2056-5968 Impact factor: 10.849