Inhibition of human cytomegalovirus proteinase by salcomine derivatives

Salcomine, N,N'-bis(salicylidene)ethylene diamino-cobalt (II), and its derivatives were evaluated for their ability to inhibit selectively human cytomegalovirus (HCMV) proteinase activity. The 50% inhibitory concentration (IC50) of salcomine was 1.4 mu M for HCMV proteinase, but >200 mu M for three other serine proteinases (trypsin, >250 mu M; chymotrypsin, 206 mu M; and elastase,: 250 mu M). Two salcomine derivatives also inhibited HCMV proteinase with IC50 values under 2 mu M. Studies of the structure-activity relationship of salcomine-related compounds showed that the phenyl moiety and the spacer moiety (distance between the two amines) were instrumental in the Inhibition of HCMV proteinase. Moreover, salcomine inhibited the growth of laboratory strain AD169 and three clinical isolates at a 50% effective concentration (EC50) range of 1.92-2.89 mu M. These results show that salcomine derivatives are potent and selective inhibitors of HCMV proteinase and HCMV replication in cell culture. Salcomine derivatives appear to be worth pursuing as candidate drugs for the chemotherapy of HCMV infection.