Two specific topoisomerase II inhibitors prevent replication of human cytomegalovirus DNA: an implied role in replication of the viral genome.
In this study, we show that human cytomegalovirus DNA synthesis is inhibited in infected confluent human embryonic lung cells treated with the DNA-intercalative topoisomerase II inhibitor 4-9'-(acridinylamino)methanesulfon-m-anisidide (m-AMSA). Similar inhibitory effects were observed with VM-26, a nonintercalative topoisomerase II inhibitor. This antiviral effect is not attributable to cytotoxic effects per se. Furthermore, m-AMSA appears to have a notably irreversible inhibitory effect on human cytomegalovirus DNA replication. No inhibition of viral DNA synthesis was observed with o-AMSA, a DNA-intercalative isomer of m-AMSA that does not inhibit topoisomerase II.
Benson
J D
JD
Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599.
Huang
E S
ES
D000677:Amsacrine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis; D006801:Humans; D013713:Teniposide / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; C033073:4'-(9-acridinylamino)methanesulfon-o-anisidide; D013713:Teniposide