Anti-herpesvirus activity of carbocyclic oxetanocin G in vitro.
A series of new compounds, carbocyclic oxetanocins, have been synthesized and their anti-herpesvirus activity determined. Carbocyclic oxetanocin G (OXT-G) was most active against herpes simplex virus (HSV) and human cytomegalovirus (HCMV) among carbocyclic oxetanocins tested; the median effective concentrations (EC50) for HSV-1, -2, and HCMV were 0.23, 0.04 and 0.40 micrograms/ml, respectively. The EC50 value of carbocyclic OXT-G against HSV-2 was significantly lower than those of acyclovir, ganciclovir (DHPG) and OXT-G, while the value for HCMV was comparable to those of DHPG and OXT-G. Carbocyclic OXT-G showed much higher activity against TK+ HSV-2 than against a TK- mutant, suggesting that this compound is a good substrate for HSV-2-induced TK. The antiviral activity of the compound was only partially reversed even by the addition of 100-fold excess deoxyguanosine. The results suggest that the mode of action of carbocyclic OXT-G is different from that of OXT-G.
Nishiyama
Y
Y
Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Yamamoto
N
N
Yamada
Y
Y
Daikoku
T
T
Ichikawa
Y
Y
Takahashi
K
K
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D018139:Simplexvirus / Q000187:drug effects*; D010948:Viral Plaque Assay
D000998:Antiviral Agents; C057479:oxetanocin G; D006147:Guanine