ALPHA,BETA-METHYLENE AND BETA,GAMMA-METHYLENE 5'-PHOSPHONATE DERIVATIVES OF 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE-5'-TRIPHOSPHATE - CORRELATION BETWEEN AFFINITY FOR REVERSE-TRANSCRIPTASE, SUSCEPTIBILITY TO HYDROLYSIS BY PHOSPHODIESTERASES AND ANTI-RETROVIRUS ACTIVITY

被引：39

作者：

BALZARINI, J ^{[1
]}

HERDEWIJN, P ^{[1
]}

PAUWELS, R ^{[1
]}

BRODER, S ^{[1
]}

DECLERCQ, E ^{[1
]}

机构：

[1] NCI, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA

来源：

BIOCHEMICAL PHARMACOLOGY | 1988年 / 37卷 / 12期

关键词：

D O I：

10.1016/0006-2952(88)90366-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A series of 5''-phosphorylated derivatives of 3''-azido-2'',3''-dideoxythymidine (AzddThd), including AzddThd 5''-mono- and 5''-triphosphate, .alpha.,.beta.-methylene AzddThd-5''-diphosphate, .alpha.,.beta.-methylene AzddThd-5''-trisphosphate, and .beta.,.gamma.-methylene AzddThd-5''-triphosphate, were evaluated for their cytostatic and anti-retrovirus properties, and their inhibitory effects on the reverse transcriptases of Moloney murine leukemia virus and human immunodeficiency virus. In contrast with the 5''-mono- and 5''-triphosphates of AzddThd, which showed cytostatic and anti-retrovirus activities comparable to those of AzddThd, the .alpha.,.beta.-methylene 5''-phosphonates of AzddThd were considerably less cytostatic and also much less inhibitory to cell transformation by Moloney murine sarcoma virus and cytopathogenicity of human immunodeficiency virus. The decreased biological activity of the phosphonate derivatives of AzddThd is most likely due to the resistance of these compounds to phosphorolytic attack by phosphodiesterases and phosphatases, and the reduced affinity for the retrovirus-associated reverse transcriptase.

引用

页码：2395 / 2403

页数：9

共 25 条

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