Inhibition of HIV‐reverse transcriptase activity by some phloroglucinol derivatives

FEBS Letters

Fujita, Akio³  Koshimura, Saburo²  Nakane, Hideo¹  Ono, Katsuhiko¹  Arisawa, Munehisa³ 

[1] Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464 Japan;Department of Serology, Kanazawa Medical University, 1-1 Daigaku, Uchinadamachi, Kahokugun, Ishikawa 920-02, Japan;Department of Medical Resources, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01 Japan

关键词: Phloroglucinol derivative;    Anti-reverse transcriptase activity;    Inhibition mechanism;    Acquired immunodeficiency syndrome;    AIDS;    acquired immunodeficiency syndrome;    ARC;    AIDS-related complex;    HIV;    liunian immunodeficiency virus;    baicalein;    5;    6;    7-trihydroxyflavone;    mallotophenone;    5-methylene-bis-2;    6-dihydroxy-3-methyl-4-methoxyacetophenone;    mallotochromene;    8-acetyl-5;    7-dihydroxy-6-(3-acetyl-2;    4-dihydroxy-5-methyl-6-methoxybenzyl)-2;    2-dimethylchromene;    mallotojaponin;    3-(3;    3-dimethylallyl)-5-(3-acetyl-2;    4-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone;    mallotolerin;    3-(3-methyl-2-hydroxy-but-3-enyl)-5-(3-acetyl-2;    4-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone;   

DOI  :  10.1016/0014-5793(91)80946-Z

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Four phloroglucinol derivatives, named mallotophenone (5-methylene-bis-2,6-dihydroxy-3-methyl-4-methoxyacetophenone), mallotochromene (8-acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6-methoxybenzyl)-2,2-dimethylchromene), mallotojaponin (3-(3,3(dimethylallyl)S-(3(acetyl-2,4-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone) and mallotolerin (3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-2,4-dihydroxy-5-methyl-6-methoxybenzyl)-phloracetophenone), have been tested for their ability to inhibit the activity of human immunodeficiency virus (HIV)-reverse transcriptase. Under the reaction conditions with (rA)_n · (dT)_12–18 as the template · primer, the enzyme activity was inhibited by approximately 70% in the presence of 10 μ/ml mallotochromene or mallotojaponin, whereas mallotophenone and mallotolerin were much less inhibitory to the enzyme. The enzyme activity was also inhibited, though to lesser extent, by these compounds under similar conditions with initiated MS-2 phage RNA as the template · primer, The mode of inhibition was, as analyzed with mallotojaponin, competivite with respect to the template · primer, (rA)_n · (dT)_12–18, and non-competitive with respect to the triphosphate substrate, dTTP, The K _i value of mallotojaponin for HIV-reverse transcriptase was determined to be 6.1 μM.

【 授权许可】

Unknown