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Colombian Contributions Fighting Leishmaniasis: A Systematic Review on Antileishmanials Combined with Chemoinformatics Analysis
Communication

Alkyl-Resorcinol Derivatives as Inhibitors of GDP-Mannose Pyrophosphorylase with Antileishmanial Activities

1
CNRS, Institut de Chimie des Substances Naturelles, Université Paris-Saclay, UPR 2301, 91198 Gif-sur-Yvette, France
2
CNRS, BioCIS, Université Paris-Saclay, 92290 Châtenay-Malabry, France
3
Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
*
Author to whom correspondence should be addressed.
Academic Editor: Susana Santos Braga
Received: 10 February 2021 / Revised: 7 March 2021 / Accepted: 9 March 2021 / Published: 11 March 2021
(This article belongs to the Special Issue Emerging molecules for leishmaniasis therapy)
Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania found in tropical and sub-tropical areas, affecting 12 million people around the world. Only few treatments are available against this disease and all of them present issues of toxicity and/or resistance. In this context, the development of new antileishmanial drugs specifically directed against a therapeutic target appears to be a promising strategy. The GDP-Mannose Pyrophosphorylase (GDP-MP) has been previously shown to be an attractive therapeutic target in Leishmania. In this study, a chemical library of 5000 compounds was screened on both L. infantum (LiGDP-MP) and human (hGDP-MP) GDP-MPs. From this screening, oncostemonol D was found to be active on both GDP-MPs at the micromolar level. Ten alkyl-resorcinol derivatives, of which oncostemonols E and J (2 and 3) were described for the first time from nature, were then evaluated on both enzymes as well as on L. infantum axenic and intramacrophage amastigotes. From this evaluation, compounds 1 and 3 inhibited both GDP-MPs at the micromolar level, and compound 9 displayed a three-times lower IC50 on LiGDP-MP, at 11 µM, than on hGDP-MP. As they displayed mild activities on the parasite, these compounds need to be further pharmacomodulated in order to improve their affinity and specificity to the target as well as their antileishmanial activity. View Full-Text
Keywords: Leishmania; therapeutic target; GDP-Mannose pyrophosphorylase; natural products; alkyl-resorcinol Leishmania; therapeutic target; GDP-Mannose pyrophosphorylase; natural products; alkyl-resorcinol
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MDPI and ACS Style

Levaique, H.; Pamlard, O.; Apel, C.; Bignon, J.; Arriola, M.; Kuhner, R.; Awang, K.; Loiseau, P.M.; Litaudon, M.; Pomel, S. Alkyl-Resorcinol Derivatives as Inhibitors of GDP-Mannose Pyrophosphorylase with Antileishmanial Activities. Molecules 2021, 26, 1551. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061551

AMA Style

Levaique H, Pamlard O, Apel C, Bignon J, Arriola M, Kuhner R, Awang K, Loiseau PM, Litaudon M, Pomel S. Alkyl-Resorcinol Derivatives as Inhibitors of GDP-Mannose Pyrophosphorylase with Antileishmanial Activities. Molecules. 2021; 26(6):1551. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061551

Chicago/Turabian Style

Levaique, Hélène, Olivier Pamlard, Cécile Apel, Jérôme Bignon, Margaux Arriola, Robin Kuhner, Khalijah Awang, Philippe M. Loiseau, Marc Litaudon, and Sébastien Pomel. 2021. "Alkyl-Resorcinol Derivatives as Inhibitors of GDP-Mannose Pyrophosphorylase with Antileishmanial Activities" Molecules 26, no. 6: 1551. https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26061551

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