Open AccessInhibition of adenosine deaminase (ADA)‐mediated metabolism of cordycepin by natural substances
Author(s) -
Li Gen,
Nakagome Izumi,
Hirono Shuichi,
Itoh Tomoo,
Fujiwara Ryoichi
Publication year - 2015
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.121
Subject(s) - cordycepin , deamination , adenosine deaminase , deoxycoformycin , naringin , chemistry , adenosine , myricetin , biochemistry , raltegravir , pharmacology , biology , kaempferol , enzyme , quercetin , antioxidant , viral load , immunology , chromatography , human immunodeficiency virus (hiv) , antiretroviral therapy
Cordycepin, which is an analogue of a nucleoside adenosine, exhibits a wide variety of pharmacological activities including anticancer effects. In this study, ADA 1‐ and ADA 2‐expressing HEK 293 cells were established to determine the major ADA isoform responsible for the deamination of cordycepin. While the metabolic rate of cordycepin deamination was similar between ADA 2‐expressing and Mock cells, extensive metabolism of cordycepin was observed in the ADA 1‐expressing cells with K m and V max values of 54.9 μ mol/L and 45.8 nmole/min/mg protein. Among five natural substances tested in this study (kaempferol, quercetin, myricetin, naringenin, and naringin), naringin strongly inhibited the deamination of cordycepin with K i values of 58.8 μ mol/L in mouse erythrocytes and 168.3 μ mol/L in human erythrocytes. A treatment of Jurkat cells with a combination of cordycepin and naringin showed significant cytotoxicity. Our in silico study suggests that not only small molecules such as adenosine derivatives but also bulky molecules like naringin can be a potent ADA 1 inhibitor for the clinical usage.