腺嘌呤衍生物的合成及体外抗疱疹病毒活性  

SYNTHESIS OF ADENINE DERIVATIVES AND THEIR ACTIVITIES AGAINST HERPES VIRUS IN VITRO

作　　者：钟蒙[1] 刘兆鹏[1] 徐丽君[1] 王志玉[1] 王桂亭[1] 

机构地区：[1]山东医科大学药学系,济南病毒教研室

出　　处：《药学学报》1996年第11期837-843,共7页Acta Pharmaceutica Sinica

摘　　要：以腺嘌呤为母体，在其９位引入活性基团Ｎ－取代缩氨基硫脲（ＴＳＣ），设计合成了１２个６－氨基－９（Ｎ４－取代乙醛缩氨基硫脲）嘌呤衍生物（４ａ～１），并进行了体外抗单纯疱疹病毒Ｉ型（ＨＳＶ－１），ＩＩ型（ＨＳＶ－２），水痘－带状疱疹病毒（ＶＺＶ）活性试验及细胞毒性试验。结果表明，除化合物４ｅ及４ｆ对ＨＳＶ－１及ＶＺＶ有较高活性外，其余化合物对上述两种病毒的活性均不明显。另外，将４ｅ与４ｆ分别与无环鸟苷（ＡＣＶ）联合用药，其最小抑制浓度（ＭＩＣ）及细胞毒性（ＭＣＣ）均显著下降。A series of 9-(N4-substituted acetaldehvde thiosemicarbazone)adenines weresynthesized and evaluated for antiherpes virus activity.Compounds 4a～1 were prepared bycondensation of 9-(acetaldehyde)adenine(6)and the corresponding N4-substituted thiosemicarbazides(10).The antiviral effects of all compounds 4a～1 were tested in vitro in primary rabbit kidney cellcultures infected with herpes simplex virus type 1(HSV-1)and varicella-herpes zOster virus(VZV),and in primary human embryo cell cultures infected with herpes simplex virus type 2 (HSV-2).Theresults showed that the minimum inhibitory concentrations(MIC)of 4e and 4f for HSV-1 and VZVwere 20,40,20 and 20 μg·ml-1,respectively,and other compounds were 200μg·ml-1.For HSV-2,the MIC of all tested compounds were 300 μg·ml-1.We also evaluated the antiherpetic effect of 4e(and 4f)by combination with acyclovir(ACV)in the ratio of 1:1 in vitro.The MIC of the combinedcompounds were 2 μg·ml-1 for 4e and 6μg·ml-1 for 4f,while their minimum cytotoxicities(MCC)in the cell were markedly reduced compared with the individual compounds.

关 键 词：腺嘌呤衍生物 缩氨基硫脲 抗疱疹病毒 合成 

分 类 号：TQ463.53[化学工程—制药化工] R978.7[医药卫生—药品]