New benzoxanthone derivatives as topoisomerase inhibitors and DNA cross-linkers

Title
New benzoxanthone derivatives as topoisomerase inhibitors and DNA cross-linkers
Author(s)
조희주[조희주]정미자[정미자]우상욱[우상욱]김정숙[김정숙]이응석권영주[권영주]나영화[나영화]
Keywords
XANTHONE DERIVATIVES; LINKING AGENTS; INSIGHT; DRUGS
Issue Date
201002
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOORGANIC & MEDICINAL CHEMISTRY, v.18, no.3, pp.1010 - 1017
Abstract
We synthesized 12 benzoxanthone derivatives classified as three different groups based on the tetracyclic ring shapes and evaluated their pharmacological activities to find potential anticancer agents. In the cytotoxicity test, most compounds showed effective cancer cell growth inhibition against the HT29 and DU145 cell lines. Among the compounds tested, compound 19 was the most effective in the cancer cell lines tested. Compound 9 showed dual inhibitory activities against DNA relaxation by topoisomerases I and II. The% inhibition of compound 9 on topoisomerase I was comparable to that of camptothecin. Compound 9 efficiently blocked topoisomerase II function by almost threefold than etoposide at 20 mu M. Compound 19 had selective topoisomerase II inhibitory activity at 100 mu M. The DNA cross-linking test revealed that only compounds 8 and 19, which possess epoxy groups, cross-linked DNA duplex, while 14 did not. From the combined pharmacological results, we proposed that the target through which compound 19 inhibits cancer cell growth may be the DNA duplex itself and/or DNA-topoisomerase II complex. (C) 2010 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/22908http://dx.doi.org/10.1016/j.bmc.2009.12.069
ISSN
0968-0896
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약학대학 > 약학부 > Articles
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