Inhibitory effects of podophyllotoxin derivatives on herpes simplex virus replication.
Podophyllotoxin and its derivatives were examined for inhibitory effects on the replication of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), including acyclovir-resistant virus and clinical isolates. Deoxypodophyllotoxin (RD4-6266) proved to be a highly potent and selective inhibitor of all HSV strains in MRC-5 cells. EC50 values of RD4-6283 (in which the methylenedioxy ring A is modified) for HSV-1 and -2 were inferior to those of deoxypodophyllotoxin. However, podorhizol (RD4-6277) and 5'-methoxy-podorhizol (RD4-6276), in which ring C is absent, did not inhibit HSV replication. Moreover, RD4-6266 also inhibited the production of infectious virus particles of HSV-1 KOS strain and HSV-2 G strain. In contrast, none of the podophyllotoxin derivatives were found to have an antiviral effect against influenza A virus, respiratory syncytial virus or human cytomegalovirus in doses not toxic to the cells.
Sudo
K
K
Rational Drug Design Laboratories, Fukushima, Japan. sudokenji@rdl.co.jp
Konno
K
K
Shigeta
S
S
Yokota
T
T
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D005562:Formazans / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D005562:Formazans; D013778:Tetrazolium Salts; C079782:MTT formazan; D011034:Podophyllotoxin