Effect of hycanthone on Schistosoma mansoni macromolecular synthesis in vitro

Adult, immature and hycanthone-resistant schistosomes were allowed to incorporate tritiated precursors of macromolecule synthesis in vitro, either in the presence of various concentrations of hycanthone, or at various times after removal of the drug. The effect on worms was compared to that on HeLa cells. The results show that hycanthone markedly inhibited the incorporation of uridine in all the systems studied, while the incorporation of thymidine and leucine was only secondarily affected. The inhibition of uridine incorporation reflected in part a decreased uptake of the radioactive precursor. The hycanthone-induced inhibition of uridine incorporation was essentially irreversible upon removal of the drug in adult schistosomes, while it was completely reversible in hycanthone-resistant worms, in immature worms and in HeLa cells. The effects of a hycanthone analog, IA-4, were largely comparable to the effects of the parent compound. These results suggest that the inhibition of RNA synthesis can be a possible explanation for the mechanism of the schistosomicidal action of hycanthone.