尿嘧啶类似物对1型人类免疫缺陷病毒及其逆转录酶的作用。

Action of uracil analogs on human immunodeficiency virus type 1 and its reverse transcriptase.

作者信息

Piras G, Dutschman G E, Im G J, Pan B C, Chu S H, Cheng Y C

机构信息

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

出版信息

Antimicrob Agents Chemother. 1995 Feb;39(2):539-41. doi: 10.1128/AAC.39.2.539.

DOI:10.1128/AAC.39.2.539

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC162575/

Abstract

Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse transcriptases resistant to nevirapine (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at position 100 to isoleucine) are cross resistant to E-BPU analogs. Nevirapine- or TIBO R82150-resistant HIV-1 were cross resistant to E-BPU analogs but were inhibited at concentrations 11- to 135-fold lower than the cytotoxic doses.

摘要

5-乙基-1-苄氧甲基-6-（苯硫基）尿嘧啶（E-BPU）的三种结构类似物在体外可抑制人类免疫缺陷病毒1型（HIV-1）复制且无细胞毒性，其效力比叠氮胸苷更强，与E-BPU效力相当。这些化合物的作用靶点是HIV-1逆转录酶。对奈韦拉平（第181位酪氨酸突变为半胱氨酸）和TIBO R82150（第100位亮氨酸突变为异亮氨酸）耐药的逆转录酶对E-BPU类似物存在交叉耐药性。对奈韦拉平或TIBO R82150耐药的HIV-1对E-BPU类似物也存在交叉耐药性，但在比细胞毒性剂量低11至135倍的浓度下受到抑制。

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