Département de chimie moléculaire

Various aza-analogs of 1,4-naphthoquinone and menadione were prepd. and tested as inhibitors and substrates of the plasmodial thioredoxin and glutathione reductases as well as the human glutathione reductase. The replacement of one to two carbons at the Ph ring of the 1,4-naphthoquinone core by one to two nitrogen atoms led to an increased oxidant character of the mols. in accordance with both the redox potential values and the substrate efficiencies. Compared to the 1,4-naphthoquinone and menadione, the quinoline-5,8-dione (I) and both quinoxaline-5,8-diones (II and III) behaved as the most efficient subversive substrates of the three NADPH-dependent disulfide reductases tested. Modulation of these parameters was obsd. by alkylation of the aza-naphthoquinone core. [on SciFinder(R)]