| Autor: |
Alex H. Y. Chan, Terence C. S. Ho, Imam Fathoni, Rebecca Pope, Kevin J. Saliba, Finian J. Leeper |
| Přispěvatelé: |
Fathoni, Imam [0000-0003-3343-8917], Saliba, Kevin J [0000-0003-3345-8440], Leeper, Finian J [0000-0003-3408-5199], Apollo - University of Cambridge Repository |
| Rok vydání: |
2023 |
| Předmět: |
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| Popis: |
Thiamine is metabolized into the coenzyme thiamine diphosphate (ThDP). Interrupting thiamine utilization leads to disease states. Oxythiamine, a thiamine analogue, is metabolized into oxythiamine diphosphate (OxThDP), which inhibits ThDP-dependent enzymes. Oxythiamine has been used to validate thiamine utilization as an anti-malarial drug target. However, high oxythiamine doses are needed in vivo because of its rapid clearance, and its potency decreases dramatically with thiamine levels. We report herein cell-permeable thiamine analogues possessing a triazole ring and a hydroxamate tail replacing the thiazolium ring and diphosphate groups of ThDP. We characterize their broad-spectrum competitive inhibition of ThDP-dependent enzymes and of Plasmodium falciparum proliferation. We demonstrate how the cellular thiamine-utilization pathway can be probed by using our compounds and oxythiamine in parallel. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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