Academic Journal
Trypanothione Metabolism as Drug Target for Trypanosomatids
| العنوان: | Trypanothione Metabolism as Drug Target for Trypanosomatids |
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| المؤلفون: | Piñeyro, María Dolores, Arias, Diego, Parodi-Talice, Adriana, Guerrero, Sergio, Robello, Carlos |
| المساهمون: | Agencia Nacional de Investigación e Innovació, Research Council of United Kingdom |
| المصدر: | Current Pharmaceutical Design ; volume 27, issue 15, page 1834-1846 ; ISSN 1381-6128 |
| بيانات النشر: | Bentham Science Publishers Ltd. |
| سنة النشر: | 2021 |
| الوصف: | Chagas Disease, African sleeping sickness, and leishmaniasis are neglected diseases caused by pathogenic trypanosomatid parasites, which have a considerable impact on morbidity and mortality in poor countries. The available drugs used as treatment have high toxicity, limited access, and can cause parasite drug resistance. Long-term treatments, added to their high toxicity, result in patients that give up therapy. Trypanosomatids presents a unique trypanothione based redox system, which is responsible for maintaining the redox balance. Therefore, inhibition of these essential and exclusive parasite’s metabolic pathways, absent from the mammalian host, could lead to the development of more efficient and safe drugs. The system contains different redox cascades, where trypanothione and tryparedoxins play together a central role in transferring reduced power to different enzymes, such as 2-Cys peroxiredoxins, non-selenium glutathione peroxidases, ascorbate peroxidases, glutaredoxins and methionine sulfoxide reductases, through NADPH as a source of electrons. There is sufficient evidence that this complex system is essential for parasite survival and infection. In this review, we explore what is known in terms of essentiality, kinetic and structural data, and the development of inhibitors of enzymes from this trypanothione-based redox system. The recent advances and limitations in the development of lead inhibitory compounds targeting these enzymes have been discussed. The combination of molecular biology, bioinformatics, genomics, and structural biology is fundamental since the knowledge of unique features of the trypanothione-dependent system will provide tools for rational drug design in order to develop better treatments for these diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.2174/1381612826666201211115329 |
| الاتاحة: | http://dx.doi.org/10.2174/1381612826666201211115329 https://www.eurekaselect.com/article/download?doi=10.2174/1381612826666201211115329 https://www.eurekaselect.com/189058/article |
| رقم الانضمام: | edsbas.EE3B99 |
| قاعدة البيانات: | BASE |
| DOI: | 10.2174/1381612826666201211115329 |
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