Evaluation of amidoxime derivatives as prodrug candidates of potent bis-cationic antimalarials
| العنوان: | Evaluation of amidoxime derivatives as prodrug candidates of potent bis-cationic antimalarials |
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| المؤلفون: | Sharon Wein, Thierry Durand, Françoise Bressolle, Séverine Denoyelle, Olivier Berger, Stéphanie Ortial, Henri Vial, Roger Escale, Yen Vo-Hoang |
| المساهمون: | Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Biomolécules et de l'Environnement (LCBE), Université Montpellier 1 (UM1)-Université de Perpignan Via Domitia (UPVD) |
| المصدر: | Bioorganic & Medicinal Chemistry Letters Bioorganic & Medicinal Chemistry Letters, 2019, 29, pp.2203-2207. ⟨10.1016/j.bmcl.2019.06.045⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Bioconversion, Plasmodium falciparum, Clinical Biochemistry, Pharmaceutical Science, 01 natural sciences, Biochemistry, Antimalarials, chemistry.chemical_compound, In vivo, Oximes, parasitic diseases, Drug Discovery, Humans, Choline, [CHIM]Chemical Sciences, Prodrugs, Molecular Biology, biology, 010405 organic chemistry, Organic Chemistry, Cationic polymerization, Prodrug, biology.organism_classification, Benzamidines, Combinatorial chemistry, In vitro, 3. Good health, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, chemistry, Molecular Medicine |
| الوصف: | Plasmodium falciparum is responsible for most of the cases of malaria and its resistance to established antimalarial drugs is a major issue. Thus, new chemotherapies are needed to fight the emerging multi-drug resistance of P. falciparum malaria, like choline analogues targeting plasmodial phospholipidic metabolism. Here we describe the synthesis of amidoxime derivatives as prodrug candidates of reverse-benzamidines and hybrid compounds able to mimic choline, as well as the design of a new series of asymmetrical bis-cationic compounds. Bioconversion studies were conducted on amidoximes in asymmetrical series and showed that amidoxime prodrug strategy could be applied on C-alkylamidine moieties, like benzamidines and that N-substituents did not alter the bioconversion of amidoximes. The antimalarial activity of the three series of compounds was evaluated in vitro against P. falciparum and in vivo against P. vinckei petteri in mice. |
| اللغة: | English |
| تدمد: | 0960-894X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1a801545a0604ede7f74093c0524614a https://hal.archives-ouvertes.fr/hal-03488325 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1a801545a0604ede7f74093c0524614a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0960894X |
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