Exploration of Fluorinated Peptoid‐Based Histone Deacetylase Inhibitors as Dual‐Stage Antiplasmodial Agents Article Swipe
Nina Reßing
,
Daniel Stopper
,
Thomas Martin Schäfer
,
Laís Pessanha de Carvalho
,
Elizabeth A. Winzeler
,
Jana Held
,
Finn K. Hansen
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/ardp.70071
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/ardp.70071
The antiplasmodial properties of a series of fluorinated peptoid‐capped histone deacetylase inhibitors (HDACi) were investigated against asexual blood stages of the drug‐sensitive 3D7 and drug‐resistant Dd2 strains of Plasmodium falciparum , as well as the exo‐erythrocytic liver stages and mature gametocytes. Among the series, compound 1h emerged as the most potent derivative, showing strong activity against both P. falciparum strains ( Pf 3D7 and Dd2 IC 50 : 0.010 μM) and Plasmodium berghei liver stages ( Pb EEF IC 50 : 0.74 μM), while lacking activity against mature gametocytes. Compound 1b was identified as a second hit compound with slightly lower activity against asexual blood and liver stages ( Pf 3D7 IC 50 : 0.019 μM; Pf Dd2 IC 50 : 0.023 μM; Pb EEF IC 50 : 2.25 μM) but showed excellent parasite selectivity (SI HepG2/3D7 : 2389; SI HepG2/Dd2 : 1973) and low single‐digit micromolar activity against mature gametocytes (IC 50 : 1.70 μM). Compared to our previous hit compound MAHA‐022, both 1b and 1h exhibited improved activity against asexual blood stages and enhanced parasite selectivity, albeit with reduced activity against liver stage parasites. Taken together, compounds 1b and 1h represent promising multi‐stage antiplasmodial HDACi scaffolds for further development and optimization.
Related Topics
Concepts
Gametocyte
Plasmodium falciparum
Histone deacetylase
Peptoid
Chemistry
Plasmodium berghei
Stereochemistry
Biology
Pharmacology
Peptide
Biochemistry
Malaria
Gene
Histone
Immunology
Metadata
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- Language
- en
- Landing Page
- https://doi.org/10.1002/ardp.70071
- OA Status
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- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413100963
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4413100963Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/ardp.70071Digital Object Identifier
- Title
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Exploration of Fluorinated Peptoid‐Based Histone Deacetylase Inhibitors as Dual‐Stage Antiplasmodial AgentsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
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2025-08-01Full publication date if available
- Authors
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Nina Reßing, Daniel Stopper, Thomas Martin Schäfer, Laís Pessanha de Carvalho, Elizabeth A. Winzeler, Jana Held, Finn K. HansenList of authors in order
- Landing page
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https://doi.org/10.1002/ardp.70071Publisher landing page
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
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https://doi.org/10.1002/ardp.70071Direct OA link when available
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Gametocyte, Plasmodium falciparum, Histone deacetylase, Peptoid, Chemistry, Plasmodium berghei, Stereochemistry, Biology, Pharmacology, Peptide, Biochemistry, Malaria, Gene, Histone, ImmunologyTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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53Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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