9-（3,4-二羟基丁基）鸟嘌呤，一种新型疱疹病毒增殖抑制剂。
9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication.
作者信息
Larsson A, Oberg B, Alenius S, Hagberg C E, Johansson N G, Lindborg B, Stening G
出版信息
Antimicrob Agents Chemother. 1983 May;23(5):664-70. doi: 10.1128/AAC.23.5.664.
Abstract
A new compound, 9-(3,4-dihydroxybutyl)guanine, has been synthesized and its antiherpes activity determined. 9-(3,4-Dihydroxybutyl)guanine was selectively phosphorylated by herpes simplex virus thymidine kinase and had a high affinity for this enzyme, with an inhibition constant of 1.5 microM. In cell culture, replication of different strains of herpes simplex virus types 1 and 2 was inhibited to the extent of 50% by 4 to 18 microM (RS)-9-(3,4-dihydroxybutyl)guanine. The (R)-enantiomer of this compound was more inhibitory than the (S)-enantiomer. Herpesvirus DNA synthesis was selectively inhibited by (RS)-9-(3,4-dihydroxybutyl)guanine in infected cells, and a low cellular toxicity was observed. (RS)-9-(3,4-Dihydroxybutyl)guanine had a therapeutic effect when applied topically to guinea pigs with cutaneous herpes simplex type 1 infections and to rabbits with herpes keratitis. Oral treatment of a generalized herpes simplex type 2 infection in mice had a therapeutic effect.
摘要
一种新的化合物9-(3,4-二羟基丁基)鸟嘌呤已被合成，并测定了其抗疱疹活性。9-(3,4-二羟基丁基)鸟嘌呤被单纯疱疹病毒胸苷激酶选择性磷酸化，且对该酶具有高亲和力，抑制常数为1.5微摩尔。在细胞培养中，4至18微摩尔的(RS)-9-(3,4-二羟基丁基)鸟嘌呤可将1型和2型单纯疱疹病毒不同毒株的复制抑制50%。该化合物的(R)-对映体比(S)-对映体更具抑制性。在感染细胞中，(RS)-9-(3,4-二羟基丁基)鸟嘌呤可选择性抑制疱疹病毒DNA合成，且观察到低细胞毒性。(RS)-9-(3,4-二羟基丁基)鸟嘌呤局部应用于患有1型皮肤单纯疱疹感染的豚鼠和患有疱疹性角膜炎的兔子时具有治疗效果。对小鼠全身性2型单纯疱疹感染进行口服治疗也具有治疗效果。
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