Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues
- Eur J Med Chem. 2010 Sep;45(9):4221-8. doi: 10.1016/j.ejmech.2010.06.017.
- 1. College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk 712-702, Republic of Korea.
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 microM 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.