ANTI-HERPESVIRUS ACTIVITY OF CARBOCYCLIC OXETANOCIN G IN VITRO

• Published in: Journal of antibiotics Vol. 42; no. 12; pp. 1854 - 1859
• Main Authors: NISHIYAMA, YUKIHIRO, YAMAMOTO, NAOHIKO, YAMADA, YOSHINARI, DAIKOKU, TOHRU, ICHIKAWA, YUH-ICHIRO, TAKAHASH, KATSUTOSHI
• Format: Journal Article
• Language: English
• Published: Japan JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1989
• Subjects: Animals; Antiviral Agents - pharmacology; Cell Line; Cercopithecus aethiops; Cytomegalovirus - drug effects; Guanine - analogs & derivatives; Guanine - pharmacology; herpes simplex virus 1; herpes simplex virus 2; Humans; Simplexvirus - drug effects; Viral Plaque Assay
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.42.1854

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 μg/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.