Pauwels R, Balzarini J, Schols D, Baba M, Desmyter J, Rosenberg I, Holy A, De Clercq E
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Antimicrob Agents Chemother. 1988 Jul;32(7):1025-30. doi: 10.1128/AAC.32.7.1025.
A study of the structure-activity relationship of a series of newly synthesized phosphonylmethoxyalkyl purine and pyrimidine derivatives revealed that several adenine derivatives substituted at the N9 position by a 2-phosphonylmethoxyethyl (PME) group inhibited human immunodeficiency virus (HIV)-induced cytopathogenicity and HIV antigen expression in vitro at concentrations significantly below the toxicity threshold for the host cells. In terms of anti-HIV potency in MT-4 cells, the PME 2,6-diaminopurine derivative (50% effective dose [ED50], 1 microM) ranked first, followed by the PME adenine derivative (ED50, 2 microM [MT-4]) and the PME 2-monoaminopurine derivative (ED50, 45 microM). Antiretroviral activity was also demonstrated in ATH8 and H9 cells, which were de novo infected with HIV, and extended to C3H mouse fibroblasts infected with Moloney murine sarcoma virus. Unlike 2',3'-dideoxyadenosine, these compounds were not found to be degraded by deaminases derived from bovine intestine.
对一系列新合成的膦酰甲氧基烷基嘌呤和嘧啶衍生物的构效关系研究表明，几种在N9位被2-膦酰甲氧基乙基（PME）基团取代的腺嘌呤衍生物，在浓度显著低于宿主细胞毒性阈值时，可在体外抑制人类免疫缺陷病毒（HIV）诱导的细胞病变效应和HIV抗原表达。就MT-4细胞中的抗HIV效力而言，PME 2,6-二氨基嘌呤衍生物（半数有效剂量[ED50]，1 microM）排名第一，其次是PME腺嘌呤衍生物（ED50，2 microM [MT-4]）和PME 2-单氨基嘌呤衍生物（ED50，45 microM）。在被HIV从头感染的ATH8和H9细胞中也证实了抗逆转录病毒活性，并扩展到感染莫洛尼鼠肉瘤病毒的C3H小鼠成纤维细胞。与2',3'-双脱氧腺苷不同，未发现这些化合物被牛肠来源的脱氨酶降解。
