PXD065399 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A novel antimalarial agent that inhibits protein synthesis in Plasmodium falciparum |
| Description | Drug resistance to nearly all antimalarials following their rollout underscores the need for novel chemotypes with novel mode of action to replenish the antimalarial drug-development pipeline. We identified a novel class of compounds in the antimalarial armory. Compound 31, characterized by a hydroxybenzamide scaffold, displays potent activity against blood-stage and late sexual stages of Plasmodium falciparum and no toxicity in human cells. Resistance selection studies with 31 identified a novel point mutation in the P. falciparum multidrug-resistance protein 1 (pfmdr1) gene, which was confirmed by CRISPR/Cas9-based gene editing as the primary mediator of resistance. Despite this, no cross-resistance towards first-line antimalarials were identified. Proteomics studies indicated that the primary mode of action of 31 is through direct binding to cytosolic ribosomal subunits, thereby inhibiting protein synthesis in the parasite. Taken together, compound 31 is a promising starting point for the development of a next-generation antimalarial. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-12-08 |
| AnnouncementXML | Submission_2025-12-07_17:14:12.152.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Lorenzo Bizzarri |
| SpeciesList | scientific name: Plasmodium falciparum NF54; NCBI TaxID: NEWT:5843; |
| ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-06-24 07:12:31 | ID requested | |
| ⏵ 1 | 2025-12-07 17:14:13 | announced | |
Publication List
| Bravo P, Diamanti E, Hamed MM, Bizzarri L, Wiedemar N, Passecker A, Brancucci NMB, Albisetti A, Gumpp C, Illarionov B, Fischer M, Witschel M, Schehl T, Hahne H, M, ä, ser P, Rottmann M, Hirsch AKH, A Novel Antimalarial Agent that Inhibits Protein Synthesis in Plasmodium falciparum. Angew Chem Int Ed Engl, 64(49):e202514085(2025) [pubmed] |
| 10.1002/anie.202514085; |
Keyword List
| submitter keyword: drug discovery, drug resistance, hydroxy benzamides,antimalarial |
Contact List
| Anna Hirsch |
|---|
| contact affiliation | Department of Pharmacy, Drug Design and Optimisation, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany |
| contact email | anna.hirsch@helmholtz-hips.de |
| lab head | |
| Lorenzo Bizzarri |
|---|
| contact affiliation | OmicScouts GmbH, Lise-Meitner-Straße 30, D-85354 Freising, Germany |
| contact email | lorenzobizzo95@gmail.com |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/12/PXD065399 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD065399
- Label: PRIDE project
- Name: A novel antimalarial agent that inhibits protein synthesis in Plasmodium falciparum
