Inhibition of leishmanial DNA synthesis by sinefungin

RNA, DNA and protein biosynthesis were studied in Leishmania donovani and L. tropica promastigotes cultured with or without sinefungin. Thymidine incorporation was significantly impaired by this compound. Neither the uptake of thymidine nor its phosphorylation were inhibited. Furthermore the ratios of deoxyribonucleotide to the corresponding ribonucleotide were not significantly affected by sinefungin. Analysis of the DNA indicates that the inhibition of thymidine incorporation affects mostly nuclear DNA, kDNA being less affected by this drug. No such effect on thymidine incorporation was observed in macrophages, the host cells of these parasites.