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Inhibition of HIV‐reverse transcriptase activity by some phloroglucinol derivatives
Author(s) -
Nakane Hideo,
Arisawa Munehisa,
Fujita Akio,
Koshimura Saburo,
Ono Katsuhiko
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80946-z
Subject(s) - reverse transcriptase , enzyme , phloroglucinol , primer (cosmetics) , chemistry , stereochemistry , microbiology and biotechnology , substrate (aquarium) , biochemistry , rna , biology , organic chemistry , ecology , gene
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.