Nishiyama Y, Yamamoto N, Yamada Y, Daikoku T, Ichikawa Y, Takahashi K
Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
J Antibiot (Tokyo). 1989 Dec;42(12):1854-9. 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 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.
一系列新的化合物——碳环氧杂环丁菌素已被合成，并测定了它们的抗疱疹病毒活性。在测试的碳环氧杂环丁菌素中，碳环氧杂环丁菌素G（OXT-G）对单纯疱疹病毒（HSV）和人巨细胞病毒（HCMV）的活性最强；HSV-1、-2和HCMV的半数有效浓度（EC50）分别为0.23、0.04和0.40微克/毫升。碳环OXT-G对HSV-2的EC50值显著低于阿昔洛韦、更昔洛韦（DHPG）和OXT-G，而对HCMV的值与DHPG和OXT-G相当。碳环OXT-G对TK+ HSV-2的活性比对TK-突变体的活性高得多，这表明该化合物是HSV-2诱导的TK的良好底物。即使加入100倍过量的脱氧鸟苷，该化合物的抗病毒活性也只是部分被逆转。结果表明，碳环OXT-G的作用方式与OXT-G不同。
