Isolation and characterization of a novel adenosine deaminase inhibitor, IADA-7, from Bacillus sp. J-89.
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.
Lee
Gwang
G
Department of Molecular Science and Technology, Ajou University, Suwon, Korea. glee@ajou.ac.kr
Lee
Sang Seop
SS
Kay
Kwang Yol
KY
Kim
Dong Wan
DW
Choi
Sangdun
S
Jun
Hong Ki
HK
D039903:Actinobacteria / Q000201:enzymology; D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001407:Bacillus / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors