Design and synthesis of amidoxime derivatives for orally potent C-alkylamidine-based antimalarial agents

Mahama Ouattara; Sharon Wein; Séverine Denoyelle; Stéphanie Ortial; Thierry Durand; Roger Escale; Henri Vial; Yen Vo-Hoang

doi:10.1016/j.bmcl.2008.12.058

Design and synthesis of amidoxime derivatives for orally potent C-alkylamidine-based antimalarial agents

Bioorg Med Chem Lett. 2009 Feb 1;19(3):624-6. doi: 10.1016/j.bmcl.2008.12.058. Epub 2008 Dec 24.

Authors

Mahama Ouattara¹, Sharon Wein, Séverine Denoyelle, Stéphanie Ortial, Thierry Durand, Roger Escale, Henri Vial, Yen Vo-Hoang

Affiliation

¹ Institut des Biomolécules Max Mousseron, UMR 5247, CNRS - Université Montpellier I - Université Montpellier II, 34093 Montpellier, France.

PMID: 19124242
DOI: 10.1016/j.bmcl.2008.12.058

Abstract

Within the frame of the design of prodrug candidates to deliver a C-alkylamidine antimalarial agent, we showed that specific O-substitutions were needed on the alkylamidoxime structure. Among the newly synthesized molecules, bis-oxadiazolone and bis-O-methylsulfonylamidoxime derivatives induced a complete clearance of parasitemia in mice after oral administration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Antimalarials / pharmacology*
Antioxidants / pharmacology*
Chemistry, Pharmaceutical / methods
Dose-Response Relationship, Drug
Drug Design
Humans
Malaria / drug therapy*
Mice
Models, Chemical
Parasitemia / drug therapy*
Plasmodium falciparum
Prodrugs

Substances

Antimalarials
Antioxidants
Prodrugs