Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents.
Fiche publication
Date publication
août 2012
Journal
Organic & biomolecular chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIOUD-CHARVET Elisabeth , Dr ELHABIRI Mourad
Tous les auteurs :
Lanfranchi DA, Cesar-Rodo E, Bertrand B, Huang HH, Day L, Johann L, Elhabiri M, Becker K, Williams DL, Davioud-Charvet E
Lien Pubmed
Résumé
Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4-naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The Ag(II)-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO(3) and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of β-hematin.
Mots clés
Animals, Antimalarials, chemical synthesis, Hemin, antagonists & inhibitors, Humans, Malaria, Falciparum, drug therapy, Methemoglobin, metabolism, Mice, Naphthoquinones, chemical synthesis, Plasmodium falciparum, drug effects, Quinolines, chemical synthesis, Schistosoma mansoni, drug effects, Schistosomiasis mansoni, drug therapy, Schistosomicides, chemical synthesis, Solubility
Référence
Org. Biomol. Chem.. 2012 Aug 21;10(31):6375-87