A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

doi:10.1038/s41421-020-00215-4

	A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1
	Huang, Zhenghui 1; Li, Ruoxi 2,3; Tang, Tongke1,4 ; Ling, Dazheng 2,3; Wang, Manjiong 2,3; Xu, Dandan 5,6; Sun, Maoxin1,4 ; Zheng, Lulu 3; Zhu, Feng 7; Min, Hui 7; Boonhok, Rachasak 7; Ding, Yan 8; Wen, Yuhao 1; Chen, Yicong 1; Li, Xiaokang 2,3; Chen, Yuxi 9; Liu, Taiping 8; Han, Jiping 1; Miao, Jun 7; Fang, Qiang 5,6; Cao, Yaming 9; Tang, Yun 3; Cui, Jie 1; Xu, Wenyue 8; Cui, Liwang 7; Zhu, Jin 2,3; Wong, Gary 1; Li, Jian 2,3; Jiang, Lubin1,4
	2020-12-11
发表期刊	CELL DISCOVERY
卷号	6 期号:1
发表状态	已发表
DOI	10.1038/s41421-020-00215-4
摘要	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.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Key R&D Program of China[2018YFA0507300] ; National Special Fund for State Key Laboratory of Bioreactor Engineering[2060204] ; National Science and Technology Major Project[2018ZX10101004003001] ; National Natural Science Foundation of China[31571345][31771455][81772218] ; National Institute of Allergy and Infectious Diseases[R01AI116466][U19AI089672]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000598238100001
出版者	SPRINGERNATURE
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/124913
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_江陆斌组生命科学与技术学院_博士生
通讯作者	Li, Jian; Jiang, Lubin
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China 2.East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China 3.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 5.Bengbu Med Coll, Dept Microbiol & Parasitol, Bengbu 233030, Anhui, Peoples R China 6.Anhui Key Lab Infect & Immun, Bengbu 233030, Anhui, Peoples R China 7.Univ S Florida, Div Infect Dis & Int Med, Dept Internal Med, Morsani Coll Med, Tampa, FL 33620 USA 8.Army Med Univ, Dept Pathogen Biol, Chongqing 400038, Peoples R China 9.China Med Univ, Coll Basic Med Sci, Dept Immunol, Shenyang 110122, Liaoning, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Huang, Zhenghui,Li, Ruoxi,Tang, Tongke,et al. A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1[J]. CELL DISCOVERY,2020,6(1).
APA	Huang, Zhenghui.,Li, Ruoxi.,Tang, Tongke.,Ling, Dazheng.,Wang, Manjiong.,...&Jiang, Lubin.(2020).A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1.CELL DISCOVERY,6(1).
MLA	Huang, Zhenghui,et al."A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1".CELL DISCOVERY 6.1(2020).