REDUCTIVE ACTIVATION OF BENZAZOLO[3,2-A]-QUINOLINIUM CHLORIDES

Initial ferricytochrome c (Cyt(III)c) reduction rates occurring in aer obic or anaerobic solutions containing either 3-nitrobenzothiazolo[3,2 -a]- (NBQCl), 1-ethyl-3-nitrobenzimidazolo[3,2-a]- (ENBIQCl), 7-ethylb enzimidazolo[3,2-a]quinolinium chloride (EHBIQCL), or nitrofurantoin ( NFT) and xanthine/xanthine oxidase were measured. Maximum rates in nit rogen-saturated solutions follow the order NFT > NBQCL > ENBIQCL > EHB IQCL. These rates correlate linearly with the half-wave reduction pote ntials (E1/2) of these compounds. With the exception of EHBIQCl, small er rates of Cyt(III)c reduction were obtained in air-saturated than in nitrogen-saturated solutions at the quinolinium salt concentrations u sed. Larger concentrations of superoxide dismutase (SOD) are needed fo r 50% inhibition of the Cyt(III)c reduction reaction for heterocyclic compounds with larger E1/2 values. Thus, measurement of the portion of the Cyt(III)c reduction rate under air that is inhibited by SOD does not account solely for the production of superoxide. These observation s suggest that NBQCL, ENBIQCl, and less probably EHBIQCl may interfere with mitochondrial energy metabolism or induce DNA damage through red uced intermediates.