Antileishmanial effect of a potent S-adenosylmethionine decarboxylase inhibitor: CGP 40215A

CGP 40215A, specific S-adenosylmethionine decarboxylase (AdoMetDC) inhibitor was found to inhibit the growth of Leishmania donovanipromastigotes (strain UR6) in a dose-dependent manner with an IC50of 18µM . The growth inhibition was reversed with 100µM of spermidine and spermine. The growth inhibitionin vitroby this inhibitor was accompanied by a significant decrease in AdoMetDC activity and spermidine levels. CGP 40215A was more potent than other AdoMetDC inhibitors, Berenil or methyl glyoxal (bis) guanyl hydrazone. The combination of CGP 40215A with other polyamine biosynthetic inhibitors like DL-α-difluoromethylornithine or the bis (benzyl) polyamine analogue (MDL 27695) shows an accentuated inhibitory effect on leishmanial growth