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Molecules ; 29(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38792079

RESUMEN

Infectious diseases caused by trypanosomatids, including African trypanosomiasis (sleeping sickness), Chagas disease, and different forms of leishmaniasis, are Neglected Tropical Diseases affecting millions of people worldwide, mainly in vulnerable territories of tropical and subtropical areas. In general, current treatments against these diseases are old-fashioned, showing adverse effects and loss of efficacy due to misuse or overuse, thus leading to the emergence of resistance. For these reasons, searching for new antitrypanosomatid drugs has become an urgent necessity, and different metabolic pathways have been studied as potential drug targets against these parasites. Considering that trypanosomatids possess a unique redox pathway based on the trypanothione molecule absent in the mammalian host, the key enzymes involved in trypanothione metabolism, trypanothione reductase and trypanothione synthetase, have been studied in detail as druggable targets. In this review, we summarize some of the recent findings on the molecules inhibiting these two essential enzymes for Trypanosoma and Leishmania viability.


Asunto(s)
Amida Sintasas , Glutatión , NADH NADPH Oxidorreductasas , Trypanosoma , NADH NADPH Oxidorreductasas/metabolismo , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , Humanos , Amida Sintasas/metabolismo , Amida Sintasas/antagonistas & inhibidores , Trypanosoma/efectos de los fármacos , Trypanosoma/metabolismo , Glutatión/metabolismo , Glutatión/análogos & derivados , Animales , Espermidina/análogos & derivados , Espermidina/metabolismo , Leishmania/efectos de los fármacos , Leishmania/metabolismo , Tripanocidas/farmacología , Tripanocidas/uso terapéutico , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/metabolismo , Leishmaniasis/parasitología , Trypanosomatina/metabolismo , Trypanosomatina/efectos de los fármacos , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/antagonistas & inhibidores , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/metabolismo
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