title: Ring fusion strategy for the synthesis of anthra[2,3-d]oxazole-2-thione-5,10-dione homologues as DNA topoisomerase inhibitors and as antitumor agents.
abstract: The efficient synthesis of mono-substituted anthraquinones and ring fusion into anthra[2,3-d]oxazole-2-thione-5,10-dione derivatives were developed, and all the compounds were tested for their cytotoxicity against PC-3 cancer cell lines. Compounds 8, 14, 17 and 23 were selected by the NCI and 12, 17 and 19 were evaluated for topoisomerase I-mediated DNA relaxation. Among them, 17 appeared to be the most active compound of this series and not only showed higher inhibition when indicated from the low IC50 values against PC-3 cancer cell line but also attenuated the in vitro topoisomerase I-mediated DNA relaxation at low micromolar concentrations. All test compounds exhibited different cytostatic and cytotoxic activities for further developing potential anticancer drugs.
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei 112, Taiwan.
authors.forename: Fei-Lan
authors.initials: FL
authors.lastname: Liu
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Tsung-Chih
authors.initials: TC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
authors.affiliation: School of Pharmacy, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ahmed Atef
authors.initials: AA
authors.lastname: Ahmed Ali
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Rheumatology/Immunology/Allergy, Taipei Veterans General Hospital, Taipei 112, Taiwan. Electronic address: ming0503@ms3.hinet.net.
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan. Electronic address: huanghs99@tmu.edu.tw.
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
mesh_terms: D000880:Anthraquinones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D010080:Oxazoles; D059003:Topoisomerase Inhibitors; D004264:DNA Topoisomerases, Type I
keywords: Anthra[2,3-d]oxazole-2-thione-5,10-dione; NCI 60-cell panel assay; Topoisomerase I-mediated DNA relaxation