FIGURE 4.

Trypanosomal type I nitroreductase-mediated nifurtimox reduction generates an unsaturated open-chain nitrile. A, HPLC trace (λ = 340 nm) of the reaction product obtained after complete reduction of nifurtimox by the trypanosomal type I nitroreductase TcNTR. TbNTR generates exactly the same metabolic profile. B, mass spectrum of the single peak obtained after HPLC. The m/z of 256 and 278 correspond to the nifurtimox-derived metabolite +H or +Na, respectively. The calculated molecular weight of 255 corresponds to an unsaturated open-chain nitrile form (see Fig. 3). C, absorption spectrum of the unsaturated open-chain nitrile product.