Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparum
Malaria tropica, caused by Plasmodium falciparum (P. falciparum), remains a global health challenge with limited therapeutic options. In mammalian cells, the small-molecule compound RAS-selective lethal 3 (RSL3) induces ferroptosis via lipid peroxidation. In this study, we demonstrate that RSL3 syne...
Gespeichert in:
| Hauptverfasser: | , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 October 2025
|
| In: |
Antimicrobial agents and chemotherapy
Year: 2025, Jahrgang: 69, Heft: 10, Pages: 1-22 |
| ISSN: | 1098-6596 |
| DOI: | 10.1128/aac.00471-25 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1128/aac.00471-25 Verlag, kostenfrei, Volltext: https://journals.asm.org/doi/10.1128/aac.00471-25 
|
| Verfasserangaben: | Vella Nikolova, Karen Linnemannstöns, Anastasiia Zahoruiko, Markus Ganter, Carsten G. Lüder, Matthias Dobbelstein |
MARC
| LEADER | 00000naa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 194857294X | ||
| 003 | DE-627 | ||
| 005 | 20260113121121.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 260113s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1128/aac.00471-25 |2 doi | |
| 035 | |a (DE-627)194857294X | ||
| 035 | |a (DE-599)KXP194857294X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Nikolova, Vella Georgieva |e VerfasserIn |0 (DE-588)137256389X |0 (DE-627)1931863628 |4 aut | |
| 245 | 1 | 0 | |a Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparum |c Vella Nikolova, Karen Linnemannstöns, Anastasiia Zahoruiko, Markus Ganter, Carsten G. Lüder, Matthias Dobbelstein |
| 246 | 3 | 0 | |a three |
| 264 | 1 | |c 1 October 2025 | |
| 300 | |b Illustrationen | ||
| 300 | |a 22 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online veröffentlicht: 18. August 2025 | ||
| 500 | |a Gesehen am 13.01.2026 | ||
| 520 | |a Malaria tropica, caused by Plasmodium falciparum (P. falciparum), remains a global health challenge with limited therapeutic options. In mammalian cells, the small-molecule compound RAS-selective lethal 3 (RSL3) induces ferroptosis via lipid peroxidation. In this study, we demonstrate that RSL3 synergizes with Pyrimethamine, an inhibitor of P. falciparum dihydrofolate reductase (DHFR), to suppress parasite proliferation in red blood cells (RBCs). A similar synergistic effect was observed with Cycloguanil, a structural analog of Pyrimethamine, but not with other DHFR inhibitors or alternative agents that induce ferroptosis in nucleated mammalian cells. Notably, Ferrostatin-1, an antagonist of lipid peroxidation, largely failed to rescue parasite growth in the presence of RSL3, possibly suggesting a mechanism distinct from canonical ferroptosis. These findings suggest that the synergy may involve unidentified targets of RSL3 and Pyrimethamine in P. falciparum, divergent from those described in mammalian systems. Moreover, RSL3 and related compounds could serve as promising adjuvants to enhance the antimalarial efficacy of Pyrimethamine and potentially overcome drug resistance. | ||
| 700 | 1 | |a Linnemannstöns, Karen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zahoruiko, Anastasiia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ganter, Markus |e VerfasserIn |0 (DE-588)138068453 |0 (DE-627)599347805 |0 (DE-576)30632072X |4 aut | |
| 700 | 1 | |a Lüder, Carsten G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dobbelstein, Matthias |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Antimicrobial agents and chemotherapy |d Washington, DC : Soc., 1972 |g 69(2025), 10 vom: Okt., Artikel-ID e00471-25, Seite 1-22 |h Online-Ressource |w (DE-627)306316919 |w (DE-600)1496156-8 |w (DE-576)09718859X |x 1098-6596 |7 nnas |a Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparum |
| 773 | 1 | 8 | |g volume:69 |g year:2025 |g number:10 |g month:10 |g elocationid:e00471-25 |g pages:1-22 |g extent:22 |a Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparum |
| 856 | 4 | 0 | |u https://doi.org/10.1128/aac.00471-25 |x Verlag |x Resolving-System |z kostenfrei |3 Volltext |7 0 |
| 856 | 4 | 0 | |u https://journals.asm.org/doi/10.1128/aac.00471-25 |x Verlag |z kostenfrei |3 Volltext |7 0 |
| 951 | |a AR | ||
| 992 | |a 20260113 | ||
| 993 | |a Article | ||
| 994 | |a 2025 | ||
| 998 | |g 138068453 |a Ganter, Markus |m 138068453:Ganter, Markus |d 910000 |d 911700 |e 910000PG138068453 |e 911700PG138068453 |k 0/910000/ |k 1/910000/911700/ |p 4 | ||
| 999 | |a KXP-PPN194857294X |e 4846086763 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Vella Nikolova, Karen Linnemannstöns, Anastasiia Zahoruiko, Markus Ganter, Carsten G. Lüder, Matthias Dobbelstein"]},"origin":[{"dateIssuedDisp":"1 October 2025","dateIssuedKey":"2025"}],"language":["eng"],"note":["Online veröffentlicht: 18. August 2025","Gesehen am 13.01.2026"],"recId":"194857294X","type":{"bibl":"article-journal","media":"Online-Ressource"},"physDesc":[{"noteIll":"Illustrationen","extent":"22 S."}],"relHost":[{"pubHistory":["1.1972 -"],"name":{"displayForm":["publ. by the American Society for Microbiology"]},"recId":"306316919","note":["Gesehen am 09.06.21"],"language":["eng"],"origin":[{"dateIssuedKey":"1972","dateIssuedDisp":"1972-","publisher":"Soc.","publisherPlace":"Washington, DC"}],"corporate":[{"display":"American Society for Microbiology","role":"isb"}],"id":{"eki":["306316919"],"issn":["1098-6596"],"zdb":["1496156-8"]},"title":[{"title_sort":"Antimicrobial agents and chemotherapy","title":"Antimicrobial agents and chemotherapy","subtitle":"AAC"}],"physDesc":[{"extent":"Online-Ressource"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"part":{"extent":"22","volume":"69","year":"2025","text":"69(2025), 10 vom: Okt., Artikel-ID e00471-25, Seite 1-22","pages":"1-22","issue":"10"},"disp":"Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparumAntimicrobial agents and chemotherapy","titleAlt":[{"title":"AAC"}]}],"title":[{"title_sort":"Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparum","title":"Synergistic activity of RSL3 and Pyrimethamine to inhibit the proliferation of Plasmodium falciparum"}],"id":{"doi":["10.1128/aac.00471-25"],"eki":["194857294X"]},"person":[{"family":"Nikolova","display":"Nikolova, Vella Georgieva","role":"aut","given":"Vella Georgieva"},{"family":"Linnemannstöns","display":"Linnemannstöns, Karen","role":"aut","given":"Karen"},{"given":"Anastasiia","role":"aut","display":"Zahoruiko, Anastasiia","family":"Zahoruiko"},{"role":"aut","given":"Markus","family":"Ganter","display":"Ganter, Markus"},{"family":"Lüder","display":"Lüder, Carsten G.","role":"aut","given":"Carsten G."},{"given":"Matthias","role":"aut","display":"Dobbelstein, Matthias","family":"Dobbelstein"}]} | ||
| SRT | |a NIKOLOVAVESYNERGISTI1202 | ||