Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agentsElectronic supplementary information (ESI) available: Experimental protocols for enzymic assays and pharmacokinetics; 1H and 13C NMR spectra of compounds 1a-d, 2a-d, 3a-d, 4a-d, and 11. See DOI: 10.1039/c2ob25812a

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 -hematin. 3-Picolinyl-menadione and quinoline-5,8-diones derivatives were evaluated for their antimalarial and antischistosomal effects.