Mucsi I, Molnár J, Motohashi N
Department of Medical Microbiology, Faculty of General Medicine, University of Szeged, 10, H-6720, Dóm tér, Hungary.
Int J Antimicrob Agents. 2001 Jul;18(1):67-72. doi: 10.1016/s0924-8579(01)00323-5.
The combined antiviral effects of some benzo[a]phenothiazines and 9-[2-hydroxy(ethoxy)methyl]guanine (acycloguanosine, acyclovir, ACV) on the multiplication of herpes simplex virus type 2 (HSV-2) were studied using Vero cells. The antiviral effect of ACV on a wild strain of HSV-2 was enhanced in the presence of 5-oxo-5H-benzo[a]phenothiazine and 6-methyl-5-oxo-5H-benzo[a]phenothiazine in a yield reduction test. A mathematical formula was used to interpret the drug interaction and a synergistic effect was found with a combination of ACV and benzo[a]phenothiazines. The effect of simultaneous application of two benzo[a]phenothiazines on the multiplication of HSV-2 strain during serial passages was also investigated. The combinations of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine with ACV at a low concentration using serial passages of a plaque-purified ACV sensitive HSV-2 strain, reduced the infective virus population. A similar effect was also found on the activity of other benzo[a]phenothiazine derivatives. When the two most effective derivatives of 5-oxo-5H-benzo[a]phenothiazine or 6-methyl-5-oxo-5H-benzo[a]phenothiazine were simultaneously used with ACV against a wild type HSV-2 strain during consecutive passages, the infective virus titres were decreased, but their effect was only moderate. These results suggest that a combination of some benzo[a]phenothiazines with ACV might enhance their antiviral activity probably by reduction of the mutagenic rate in the virus populations.
使用非洲绿猴肾细胞（Vero细胞）研究了某些苯并[a]吩噻嗪与9-[2-羟基（乙氧基）甲基]鸟嘌呤（阿昔洛韦）对单纯疱疹病毒2型（HSV-2）增殖的联合抗病毒作用。在蚀斑减少试验中，5-氧代-5H-苯并[a]吩噻嗪和6-甲基-5-氧代-5H-苯并[a]吩噻嗪存在时，阿昔洛韦对HSV-2野生株的抗病毒作用增强。用数学公式解释药物相互作用，发现阿昔洛韦与苯并[a]吩噻嗪联合具有协同作用。还研究了两种苯并[a]吩噻嗪同时应用对HSV-2毒株连续传代增殖的影响。使用蚀斑纯化的对阿昔洛韦敏感的HSV-2毒株连续传代，5-氧代-5H-苯并[a]吩噻嗪或6-甲基-5-氧代-5H-苯并[a]吩噻嗪与低浓度阿昔洛韦联合，可减少感染性病毒数量。在其他苯并[a]吩噻嗪衍生物的活性上也发现了类似效果。当5-氧代-5H-苯并[a]吩噻嗪或6-甲基-5-氧代-5H-苯并[a]吩噻嗪的两种最有效衍生物在连续传代过程中与阿昔洛韦同时用于对抗野生型HSV-2毒株时，感染性病毒滴度降低，但效果仅为中等。这些结果表明，某些苯并[a]吩噻嗪与阿昔洛韦联合可能通过降低病毒群体中的诱变率来增强其抗病毒活性。
