Watanabe S, Konno K, Shigeta S, Yokota T
Rational Drug Design Laboratories, Fukushima, Japan.
Antivir Chem Chemother. 1998 May;9(3):269-74. doi: 10.1177/095632029800900308.
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 microM for HCMV proteinase, but > 200 microM for three other serine proteinases (trypsin, > 250 microM; chymotrypsin, 206 microM; and elastase, > 250 microM). Two salcomine derivatives also inhibited HCMV proteinase with IC50 values under 2 microM. 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 microM. 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.
对水杨醛钴（II），即N，N'-双（水杨基亚乙基）乙二胺钴及其衍生物抑制人巨细胞病毒（HCMV）蛋白酶活性的能力进行了评估。水杨醛钴对HCMV蛋白酶的50%抑制浓度（IC50）为1.4微摩尔，但对其他三种丝氨酸蛋白酶（胰蛋白酶，>250微摩尔；糜蛋白酶，206微摩尔；弹性蛋白酶，>250微摩尔）则>200微摩尔。两种水杨醛钴衍生物也能抑制HCMV蛋白酶，其IC50值低于2微摩尔。对与水杨醛钴相关化合物的构效关系研究表明，苯基部分和间隔部分（两个胺之间的距离）对抑制HCMV蛋白酶起重要作用。此外，水杨醛钴在1.92 - 2.89微摩尔的50%有效浓度（EC50）范围内抑制实验室菌株AD169和三种临床分离株的生长。这些结果表明，水杨醛钴衍生物是细胞培养中HCMV蛋白酶和HCMV复制的有效且选择性抑制剂。水杨醛钴衍生物似乎值得作为HCMV感染化疗的候选药物进行研究。
