Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei
Trypanosomiasis is a parasitic disease for which new treatments are needed due to the frequent occurrence of adverse side effects of current available drugs. Natural compounds found in traditionally used plants offer opportunities to discover innovative compounds that could prove pivotal to antitryp...
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| Format: | Article |
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Elsevier
2025-08-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320725000181 |
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| author | Lúcia Mamede Fanta Fall Madeline Vast Kristelle Hughes Giorgia Martelli Francesco Caligiore Bernadette Govaerts Paul A.M. Michels Michel Frédérich Joëlle Quetin-Leclercq |
| author_facet | Lúcia Mamede Fanta Fall Madeline Vast Kristelle Hughes Giorgia Martelli Francesco Caligiore Bernadette Govaerts Paul A.M. Michels Michel Frédérich Joëlle Quetin-Leclercq |
| author_sort | Lúcia Mamede |
| collection | DOAJ |
| description | Trypanosomiasis is a parasitic disease for which new treatments are needed due to the frequent occurrence of adverse side effects of current available drugs. Natural compounds found in traditionally used plants offer opportunities to discover innovative compounds that could prove pivotal to antitrypanosomal drug development. 3-O-p-(Z/E)-coumaroyltormentic acids (CTA) were isolated first from the West Africa-native tree Vitellaria paradoxa and have demonstrated quite selective in vitro and in vivo antitrypanosomal activity, despite the unknown mode of action. In this study, a metabolomics analysis using the data from both LC-HR-MS and 1H-NMR described CTA's effects on Trypanosoma brucei after 3 h exposure under 5 or 10 x EC50. Our study shows CTA's activity impacted tryptophan metabolism and reveals potential targets in different branches of this metabolism. Our results demonstrate a likely presence of enzymes dedicated to tryptophan, like a tryptophan aminotransferase, tryptophan 2,3-dioxygenase and/or indoleamine 2,3-dioxygenase, and other enzymes of the kynurenine pathway, despite the absence of their description thus far in this species. These data further implicate that CTA's toxic effect on the tryptophan metabolism may be attributed to the decrease of the intracellular level of essential aspartate, resulting from inhibition of its aminotransferase. In resume, our study shines light on the likelihood of the tryptophan metabolism pathway presenting innovative targets toward the development of antitrypanosomal drugs. These require confirmation through functional and enzymatic studies. |
| format | Article |
| id | doaj-art-d392ae22f55249b086d1c8f9bf26e0cf |
| institution | Kabale University |
| issn | 2211-3207 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj-art-d392ae22f55249b086d1c8f9bf26e0cf2025-08-20T04:01:48ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072025-08-012810059510.1016/j.ijpddr.2025.100595Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei bruceiLúcia Mamede0Fanta Fall1Madeline Vast2Kristelle Hughes3Giorgia Martelli4Francesco Caligiore5Bernadette Govaerts6Paul A.M. Michels7Michel Frédérich8Joëlle Quetin-Leclercq9Pharmacognosy Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Brussels, Belgium; Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium; Corresponding author.Pharmacognosy Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Brussels, BelgiumInstitute of Statistics, Biostatistics and Actuarial Sciences (ISBA/LIDAM), Université catholique de Louvain (UCLouvain), Louvain-la-Neuve, BelgiumPharmacognosy Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Brussels, BelgiumPharmacognosy Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Brussels, Belgiumde Duve Institute and WELBIO, UCLouvain, Avenue Hippocrate 75, 1200, Brussels, BelgiumInstitute of Statistics, Biostatistics and Actuarial Sciences (ISBA/LIDAM), Université catholique de Louvain (UCLouvain), Louvain-la-Neuve, BelgiumSchool of Biological Sciences, The University of Edinburgh, Scotland, UKLaboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, BelgiumPharmacognosy Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Brussels, BelgiumTrypanosomiasis is a parasitic disease for which new treatments are needed due to the frequent occurrence of adverse side effects of current available drugs. Natural compounds found in traditionally used plants offer opportunities to discover innovative compounds that could prove pivotal to antitrypanosomal drug development. 3-O-p-(Z/E)-coumaroyltormentic acids (CTA) were isolated first from the West Africa-native tree Vitellaria paradoxa and have demonstrated quite selective in vitro and in vivo antitrypanosomal activity, despite the unknown mode of action. In this study, a metabolomics analysis using the data from both LC-HR-MS and 1H-NMR described CTA's effects on Trypanosoma brucei after 3 h exposure under 5 or 10 x EC50. Our study shows CTA's activity impacted tryptophan metabolism and reveals potential targets in different branches of this metabolism. Our results demonstrate a likely presence of enzymes dedicated to tryptophan, like a tryptophan aminotransferase, tryptophan 2,3-dioxygenase and/or indoleamine 2,3-dioxygenase, and other enzymes of the kynurenine pathway, despite the absence of their description thus far in this species. These data further implicate that CTA's toxic effect on the tryptophan metabolism may be attributed to the decrease of the intracellular level of essential aspartate, resulting from inhibition of its aminotransferase. In resume, our study shines light on the likelihood of the tryptophan metabolism pathway presenting innovative targets toward the development of antitrypanosomal drugs. These require confirmation through functional and enzymatic studies.http://www.sciencedirect.com/science/article/pii/S2211320725000181Metabolomics3-O-p-E/Z-coumaroyltormentic acidsTrypanosoma brucei bruceiMass spectrometryNuclear Magnetic Resonance |
| spellingShingle | Lúcia Mamede Fanta Fall Madeline Vast Kristelle Hughes Giorgia Martelli Francesco Caligiore Bernadette Govaerts Paul A.M. Michels Michel Frédérich Joëlle Quetin-Leclercq Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei International Journal for Parasitology: Drugs and Drug Resistance Metabolomics 3-O-p-E/Z-coumaroyltormentic acids Trypanosoma brucei brucei Mass spectrometry Nuclear Magnetic Resonance |
| title | Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei |
| title_full | Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei |
| title_fullStr | Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei |
| title_full_unstemmed | Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei |
| title_short | Metabolomics study of 3-O-p-(Z/E)-coumaroyltormentic acid-treated Trypanosoma brucei brucei |
| title_sort | metabolomics study of 3 o p z e coumaroyltormentic acid treated trypanosoma brucei brucei |
| topic | Metabolomics 3-O-p-E/Z-coumaroyltormentic acids Trypanosoma brucei brucei Mass spectrometry Nuclear Magnetic Resonance |
| url | http://www.sciencedirect.com/science/article/pii/S2211320725000181 |
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