Structural insights into the Plasmodium falciparum histone deacetylase 1 (PfHDAC-1): A novel target for the development of antimalarial therapy

2008 ◽  
Vol 16 (9) ◽  
pp. 5254-5265 ◽  
Author(s):  
Prasenjit Mukherjee ◽  
Anupam Pradhan ◽  
Falgun Shah ◽  
Babu L. Tekwani ◽  
Mitchell A. Avery
Keyword(s):  
Plasmodium Falciparum ◽  
Histone Deacetylase ◽  
Histone Deacetylase 1 ◽  
Antimalarial Therapy ◽  
Novel Target ◽  
Structural Insights

scholarly journals Proteomic analysis of Plasmodium falciparum histone deacetylase 1 complex proteins

2019 ◽  
Vol 198 ◽  
pp. 7-16 ◽  
Author(s):  
Jessica A. Engel ◽  
Emma L. Norris ◽  
Paul Gilson ◽  
Jude Przyborski ◽  
Addmore Shonhai ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Histone Deacetylase ◽  
Proteomic Analysis ◽  
Histone Deacetylase 1

scholarly journals Valproic Acid as a Potential Inhibitor of Plasmodium falciparum Histone Deacetylase 1 (PfHDAC1): An in Silico Approach

2015 ◽  
Vol 16 (2) ◽  
pp. 3915-3931 ◽  
Author(s):  
Mohamed Elbadawi ◽  
Mohamed Awadalla ◽  
Muzamil Hamid ◽  
Magdi Mohamed ◽  
Talal Awad
Keyword(s):  
Valproic Acid ◽  
Plasmodium Falciparum ◽  
Histone Deacetylase ◽  
In Silico ◽  
Histone Deacetylase 1 ◽  
Potential Inhibitor

scholarly journals A novel multistage antiplasmodial inhibitor targeting Plasmodium falciparum histone deacetylase 1

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhenghui Huang ◽  
Ruoxi Li ◽  
Tongke Tang ◽  
Dazheng Ling ◽  
Manjiong Wang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Multidrug Resistance ◽  
Histone Deacetylase ◽  
Malaria Parasites ◽  
Histone Deacetylase 1 ◽  
Life Cycle Stages ◽  
Deacetylase Inhibitor ◽  
Transcriptomic Changes ◽  
Artemisinin Combination Therapies

AbstractAlthough 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.

Kinetic and structural insights into the binding of histone deacetylase 1 and 2 (HDAC1, 2) inhibitors

2016 ◽  
Vol 24 (18) ◽  
pp. 4008-4015 ◽  
Author(s):  
Florence F. Wagner ◽  
Michel Weïwer ◽  
Stefan Steinbacher ◽  
Adrian Schomburg ◽  
Peter Reinemer ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase 1 ◽  
Structural Insights

Structural Studies of Aminopeptidase P from Plasmodium falciparum: A Novel Target Against Malaria

2017 ◽  
Vol 14 (3) ◽  
pp. 330-338
Author(s):  
Polaboina Snigdha ◽  
Pachineella Rao ◽  
Nagu Prabhu ◽  
Insaf Qureshi
Keyword(s):  
Plasmodium Falciparum ◽  
Structural Studies ◽  
Aminopeptidase P ◽  
Novel Target

scholarly journals 8a, a New Acridine Antiproliferative and Pro-Apoptotic Agent Targeting HDAC1/DNMT1

2021 ◽  
Vol 22 (11) ◽  
pp. 5516
Author(s):  
Qiting Zhang ◽  
Ziyan Wang ◽  
Xinyuan Chen ◽  
Haoxiang Qiu ◽  
Yifan Gu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Hdac Inhibitors ◽  
Mitochondrial Pathway ◽  
Epigenetic Therapy ◽  
Protein Interaction Data ◽  
Dependent Manner ◽  
Histone Deacetylase 1 ◽  
Histiocytic Lymphoma ◽  
Dose Dependent

Epigenetic therapy using histone deacetylase (HDAC) inhibitors has become an attractive project in new drug development. However, DNA methylation and histone acetylation are important epigenetic ways to regulate the occurrence and development of leukemia. Given previous studies, N-(2-aminophenyl)benzamide acridine (8a), as a histone deacetylase 1 (HDAC1) inhibitor, induces apoptosis and shows significant anti-proliferative activity against histiocytic lymphoma U937 cells. HDAC1 plays a role in the nucleus, which we confirmed by finding that 8a entered the nucleus. Subsequently, we verified that 8a mainly passes through the endogenous (mitochondrial) pathway to induce cell apoptosis. From the protein interaction data, we found that 8a also affected the expression of DNA methyltransferase 1 (DNMT1). Therefore, an experiment was performed to assess the binding of 8a to DNMT1 at the molecular and cellular levels. We found that the binding strength of 8a to DNMT1 enhanced in a dose-dependent manner. Additionally, 8a inhibits the expression of DNMT1 mRNA and its protein. These findings suggested that the anti-proliferative and pro-apoptotic activities of 8a against leukemia cells were achieved by targeting HDAC1 and DNMT1.

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