title: Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents.
abstract: 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.
authors: European School of Chemistry, Polymers and Materials (ECPM) University of Strasbourg, UMR CNRS 7509, 25 Rue Becquerel, F-67087 Strasbourg, France.
authors: Don Antoine
authors: DA
authors: Lanfranchi
authors: Elena
authors: E
authors: Cesar-Rodo
authors: Benoît
authors: B
authors: Bertrand
authors: Hsin-Hung
authors: HH
authors: Huang
authors: Latasha
authors: L
authors: Day
authors: Laure
authors: L
authors: Johann
authors: Mourad
authors: M
authors: Elhabiri
authors: Katja
authors: K
authors: Becker
authors: David L
authors: DL
authors: Williams
authors: Elisabeth
authors: E
authors: Davioud-Charvet
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006427:Hemin / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D008706:Methemoglobin / Q000378:metabolism; D051379:Mice; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy; D012556:Schistosomicides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility
chemical_list: D000962:Antimalarials; D009285:Naphthoquinones; D011804:Quinolines; D012556:Schistosomicides; D006427:Hemin; D008706:Methemoglobin; C035342:1,4-naphthoquinone