Isolation and characterization of a novel adenosine deaminase inhibitor, IADA-7, from Bacillus sp. J-89.

Abstract

Adenosine deaminase (ADA), an enzyme involved in purine metabolism, catalyzes the hydrolytic breakdown of adenosine into inosine and free ammonia. ADA regulation has been targeted as a potential therapeutic agent for viral infections and lymphoproliferative disorders. In this study, we isolated a novel ADA inhibitor from a culture of Bacillus sp. J-89, and evaluated its anti-proliferative activity on human cancer cell lines. The ADA inhibitor was deduced as a 2-N-methyl-2,4-diazacycloheptanone by analyses of UV, IR, EI-MASS, (1)H-NMR, (13)C-(1)H NMR, and (13)C-NMR spectroscopy, and was designated IADA-7. IADA-7 was shown to inhibit purified mammalian and Actinomyces ADA. IADA-7 also inhibited the proliferation of both Jurkat T cells (IC(50) = 15 microg/mL) and J 82 (human transitional-cell carcinoma, bladder) cells (IC(50) = 25 microg/mL). In Jurkat T cells, apoptosis with 15 microg/mL IADA-7 for 24 and 48 hours was 9 and 13%, respectively. These results suggest that IADA-7 can inhibit ADA activity in multiple species and that it may represent a good candidate as an anti-cancer therapeutic agent due to its demonstrated anti-proliferative activity on cancer cells.