Leishmania infantum promastigotes: effects of diamidines on DNA synthesis and non-protein thiol contents

We have compared the antiproliferative activity of eight diamidines and two inhibitors of polyamine synthesis on Leishmania infantum promastigotes to their action on the cell cycle and non-protein thiol contents. As expected, both diamidines and polyamine synthesis inhibitors induced an exponential dose-related decrease in growth, a concomitant fall in non-protein thiol co ntents and a significant inhibition of DNA synthesis. However, in contrast to the inhibitors of polyamine synthesis, which reduced the percentages of cells in the S phase of the cell cycle only at high concentrations, diamidi nes inhibited DNA synthesis at infinitesimal concentrations. There was also a strong correlation between the S-phase decline and inhibition of growth. This suggests that DNA synthesis inhibition due to diamidine treatment cou ld not be considered as a side-effect resulting from polyamine depletion, b ut may be the principal mechanism of diamidine antiproliferative activity i n Leishmania promastigotes. Med Sci Res 27:149-152 (C) 1999 Lippincott Will iams & Wilkins.