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

Authors
Lee, G; Lee, SS; Kay, KY; Kim, DW; Choi, S; Jun, HK
Citation
Journal of enzyme inhibition and medicinal chemistry, 24(1):59-64, 2009
Journal Title
Journal of enzyme inhibition and medicinal chemistry
ISSN
1475-63661475-6374
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.
MeSH terms
Actinobacteria/enzymologyAdenosine Deaminase/antagonists & inhibitors*Antineoplastic Agents/chemistryAntineoplastic Agents/isolation & purificationAntineoplastic Agents/pharmacologyBacillus/chemistry*Cell Line, TumorCell Proliferation/drug effectsEnzyme Inhibitors/chemistryEnzyme Inhibitors/isolation & purification*Enzyme Inhibitors/pharmacologyHumansInhibitory Concentration 50Molecular Structure
DOI
10.1080/14756360801906863
PMID
18608782
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Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
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