title: Structure-based hybridization, synthesis and biological evaluation of novel tetracyclic heterocyclic azathioxanthone analogues as potential antitumor agents.
abstract: A series of tetracyclic heterocyclic azathioxanthones were synthesized and evaluated for cell proliferations, topoisomerase inhibitions, and NCI-60 cell panel assay, respectively. Compounds 5, 7, 8, 16, and 19 were selected for topoisomerase assay after MTT assay. 7 not only showed cytotoxic effect (IC50 = 2.84 ± 0.64 μM) in PC-3 cells but also revealed topoisomerases inhibition with IC50 (10-25 μM) and increased apoptotic cleavage of PARP and caspase 3 activity. The overall of novel azathioxanthones with different cytostatic and cytotoxic activities should be further developed as new potential candidates for anticancer drugs.
authors: 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: Tsung-Chih
authors: TC
authors: Chen
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors: Chia-Lun
authors: CL
authors: Wu
authors: 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: Chia-Chung
authors: CC
authors: Lee
authors: 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: Chun-Liang
authors: CL
authors: Chen
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; Uro-Oncology Laboratory, Division of Urology, Department of Surgery, Tri-Service General Hospital, Taipei 114, Taiwan. Electronic address: yuds@ms21.hinet.net.
authors: Dah-Shyong
authors: DS
authors: Yu
authors: 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; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan. Electronic address: huanghs99@gmail.com.
authors: Hsu-Shan
authors: HS
authors: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013892:Thioxanthenes / Q000737:chemistry* / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000607152:10-chloro-6-(piperazin-1-yl)-12H-thiochromeno(2,3-c)quinolin-12-one; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D011804:Quinolines; D013892:Thioxanthenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: Azathioxanthones; Cytostatic and cytotoxic activities; MTT assay; NCI-60 human tumor cell lines; Topoisomerase assays