ArticleAntimicrobial agents and chemotherapy2014
Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Hydroxamic Acids as HDAC Inhibitor Drug Leads for Malaria.Medicinal research reviews · 2026Review
- Molecular mechanisms involved inFrontiers in microbiology · 2026Review
- Elevated NADNature communications · 2025Article
- Epigenetic regulation as a therapeutic target in the malaria parasite Plasmodium falciparum.Malaria journal · 2024Review
- New Transmission-Selective Antimalarial Agents through Hit-to-Lead Optimization of 2-([1,1'-Biphenyl]-4-carboxamido)benzoic Acid Derivatives.Chembiochem : a European journal of chemical biology · 2022Article
- Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183.Nature communications · 2022Article
- Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.PLoS pathogens · 2021Review
- Beyond phosphorylation: Putative roles of post-translational modifications in Plasmodium sexual stages.Molecular and biochemical parasitology · 2021Article
- Organoarsenic Compounds with In Vitro Activity against the Malaria ParasiteBiomedicines · 2020Article
- Activity of Epigenetic Inhibitors against Plasmodium falciparum Asexual and Sexual Blood Stages.Antimicrobial agents and chemotherapy · 2020Article
- Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii.BMC biology · 2020Article
- Disruption of theACS infectious diseases · 2020Article
- Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites.Scientific reports · 2020Article
- Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites.Nucleic acids research · 2020Article
- Primaquine derivatives: Modifications of the terminal amino group.European journal of medicinal chemistry · 2019Review
- Structure-Activity and Structure-Toxicity Relationships of Peptoid-Based Histone Deacetylase Inhibitors with Dual-Stage Antiplasmodial Activity.ChemMedChem · 2019Article
- Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasiteEMBO reports · 2019Article
- One-pot, multi-component synthesis and structure-activity relationships of peptoid-based histone deacetylase (HDAC) inhibitors targeting malaria parasites.European journal of medicinal chemistry · 2018Article
- SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents.ChemistryOpen · 2018Article
- Post-translational modifications as key regulators of apicomplexan biology: insights from proteome-wide studies.Molecular microbiology · 2018Review
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including asexual stage malaria parasites. Here we confirm the expression of at least one HDAC protein in Plasmodium falciparum gametocytes and show that histone and nonhistone protein acetylation occurs in this life cycle stage. The activity of the canonical HDAC inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes and on gamete formation was examined. Several compounds displayed early/late-stage gametocytocidal activity, with TSA being the most potent (50% inhibitory concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode of action targeting HDAC activity. Our data identify HDAC inhibitors as being among a limited number of compounds that target both asexual and sexual stage malaria parasites, making them a potential new starting point for gametocytocidal drug leads and valuable tools for dissecting gametocyte biology.
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