title: Synthesis and in vitro evaluation of 1,8-diazaanthraquinones bearing 3-dialkylaminomethyl or 3-(N-alkyl- or N-aryl)carbamoyloxymethyl substituent.
abstract: A series of 1,8-diazaanthraquinone derivatives carrying a 3-dialkylaminomethyl or a 3-(N-alkyl or aryl)carbamoyloxymethyl substituent was synthesised and their in vitro cytotoxic activities were evaluated against eight human cancer cell lines (HOP62, SK-OV-3, HCT-15, SF295, MCF7, SNU-354, KB-3-1 and KB-V-1). A number of compounds including 8c, 8d and 11c showed cytotoxic activity comparable to that of doxorubicin against all human cancer cell lines tested. The compounds 8c and 8d were 2-100 times more potent than doxorubicin against HCT-15, MCF7 and SNU-354 cancer cell lines. Furthermore, these compounds retained considerable cytotoxic activity against the doxorubicin-resistant cell line KB-V-1, implying their therapeutic potential to treat doxorubicin-resistant tumours. These compounds inhibited topoisomerase II-mediated DNA relaxation in vitro, suggesting that this inhibitory effect be attributable to their cytotoxicity.
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk 361-763, Cheongju, South Korea. medchem@trut.chungbuk.ac.kr
authors.forename: Heesoon
authors.initials: H
authors.lastname: Lee
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Lee
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
authors.forename: Sang Un
authors.initials: SU
authors.lastname: Choi
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Yang
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin