TY - JOUR
T1 - Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues
AU - Woo, Sangwook
AU - Kang, Da Hye
AU - Nam, Jung Min
AU - Lee, Chong Soon
AU - Ha, Eun Mi
AU - Lee, Eung Seok
AU - Kwon, Youngjoo
AU - Na, Younghwa
N1 - Funding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2006-521-E00159 ). J.M.N. was partially supported by the Brain Korea 21 project.
PY - 2010/9
Y1 - 2010/9
N2 - In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 μM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds. In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives.
AB - In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives. In the cytotoxicity test, compounds 17 and 31 exhibited 2- to 7-fold stronger inhibitory activity than adriamycin against most cancer cell lines tested. Halohydrin group-tethered compounds 19, 21 and 27 showed comparable topoisomerase II inhibitory activity to etoposide at 100 μM concentration. In the DNA cross-linking test, compounds 20, 30 and 31 produced DNA cross-linked adducts and compound 30 was the strongest DNA cross-linker. Based on the combined pharmacological results, we suspected that the strong anti-cancer activity of compounds 16, 17, 20, 30 and 31 originated from the DNA mono-alkylation or cross-linking properties of the compounds. In order to develop potential anti-cancer agents that act on topoisomerase II and DNA, we have synthesized 12 new xanthone derivatives.
KW - Anticancer activities
KW - DNA cross-linking
KW - Methyloxiranylmethoxyxanthones
KW - Oxiranylmethoxyxanthones
KW - Topoisomerase II inhibition
UR - http://www.scopus.com/inward/record.url?scp=77955551433&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2010.06.017
DO - 10.1016/j.ejmech.2010.06.017
M3 - Article
C2 - 20619511
AN - SCOPUS:77955551433
SN - 0223-5234
VL - 45
SP - 4221
EP - 4228
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 9
ER -
