title: Synthesis and pharmacological evaluation of new methyloxiranylmethoxyxanthone analogues.
abstract: 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.
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Sangwook
authors.initials: S
authors.lastname: Woo
authors.forename: Da-hye
authors.initials: DH
authors.lastname: Kang
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Nam
authors.forename: Chong Soon
authors.initials: CS
authors.lastname: Lee
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Ha
authors.forename: Eung-Seok
authors.initials: ES
authors.lastname: Lee
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Na
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D059005:Topoisomerase II Inhibitors; D044004:Xanthones; D004247:DNA; C009689:xanthone; D004250:DNA Topoisomerases, Type II