Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 183, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.111660
Keywords
Leishmanicidal drugs; Miltefosine; Amphotericin B; Fluconazole; ltraconazole; Posaconazole
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Funding
- Fundacao para a Ciencia e a Tecnologia (FCT, Portugal)
- European Union
- QREN
- European Fund for Regional Development (FEDER), through the programme COMPETE [PEst C-QUI/UI0062/2019, FCOMP-01-0124-FEDER-037296]
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This mini-review focuses on leishmanicidal drugs that were sourced from small molecules previously approved for other diseases. The mechanisms of action of these molecules are herein explored, to probe the origins of their inter-species growth inhibitory activities. It is shown how the transversal action of the azoles - fluconazole, posaconazole and itraconazole - in both fungi and Leishmania is due to the occurrence of the same target, lanosterol 14-alpha-demethylase, in these two groups of species. In turn, the drugs miltefosine and amphotericin B are presented as truly multi-target agents, acting on small molecules, proteins, genes and even organelles. Steps towards future leishmanicidal drug candidates based on the multi-target strategy and on drug repurposing are also briefly presented. (C) 2019 Elsevier Masson SAS. All rights reserved.
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