Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it. is important to know the mec hanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-ph enylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds d iffered in the precise mode of action. The inhibitory effect of I on the ac tivity of the eukaryotic elongation factor eEF-2 and ribosomes seems to sug gest that the binding site of eEF-2 on the ribosome was blocked by this com pound, eEF-2 has been identified as the primary target of II and eEF-1 as t he primary target of DAPI in the system studied.