Title :

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

Author(s) :

Levaique, Hélène [Auteur]
Institut de Chimie des Substances Naturelles [ICSN]
Pamlard, Olivier [Auteur]
Unité de Catalyse et Chimie du Solide (UCCS) - UMR 8181
Apel, Cécile [Auteur]
Institut de Chimie des Substances Naturelles [ICSN]
Bignon, Jérôme [Auteur]
Institut de Chimie des Substances Naturelles [ICSN]
Arriola, Margaux [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Kuhner, Robin [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Awang, Khalijah [Auteur]
University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] [UM]
Loiseau, Philippe M. [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]
Litaudon, Marc [Auteur]
Institut de Chimie des Substances Naturelles [ICSN]
Pomel, Sébastien [Auteur]
Biomolécules : Conception, Isolement, Synthèse [BioCIS]

Journal title :

Molecules

Abbreviated title :

Molecules

Volume number :

26

Pages :

1551

Publication date :

2021-03-11

ISSN :

1420-3049

HAL domain(s) :

Chimie

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CNRS
Centrale Lille
ENSCL
Univ. Artois
Université de Lille

Collections :

• Unité de Catalyse et Chimie du Solide (UCCS) - UMR 8181

Submission date :

2022-03-24T09:02:43Z
2023-01-11T10:34:09Z