Nasr M, Drach J C, Smith S H, Shipman C, Burckhalter J H
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109.
J Med Chem. 1988 Jul;31(7):1347-51. doi: 10.1021/jm00402a016.
A series of 7-aminoquinoline derivatives was synthesized and evaluated for their capacity to produce cytotoxicity in KB cells and to inhibit the replication of herpes simplex virus (HSV) type 1. All compounds tested inhibited the replication of HSV-1 with 50% inhibitory concentrations in the range of 2-50 micrograms/mL. The antiviral activity of many compounds, however, was separated from cytotoxicity to replicating uninfected cells by only two- to fivefold higher than those required for antiviral activity. Nonetheless, six compounds (10, 28, 29, 32, 34, and 36) were identified in which the separation was greater than fivefold. All compounds examined were more potent inhibitors of viral DNA synthesis than the cellular DNA synthesis.
合成了一系列7-氨基喹啉衍生物，并评估了它们在KB细胞中产生细胞毒性以及抑制单纯疱疹病毒1型（HSV-1）复制的能力。所有测试的化合物均能抑制HSV-1的复制，其50%抑制浓度范围为2至50微克/毫升。然而，许多化合物的抗病毒活性与对未感染复制细胞的细胞毒性之间的分离倍数仅比抗病毒活性所需浓度高两到五倍。尽管如此，还是鉴定出了六种化合物（10、28、29、32、34和36），其分离倍数大于五倍。所有检测的化合物对病毒DNA合成的抑制作用比对细胞DNA合成的抑制作用更强。
