7-Aminoquinolines. A novel class of agents active against herpesviruses.
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.
Nasr
M
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Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109.
Drach
J C
JC
Smith
S H
SH
Shipman
C
C
Burckhalter
J H
JH
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000096:biosynthesis; D014176:Protein Biosynthesis; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000634:Aminoquinolines; D000998:Antiviral Agents; D014764:Viral Proteins; D004247:DNA