title: Structure-based design, synthesis and evaluation of novel anthra[1,2-d]imidazole-6,11-dione derivatives as telomerase inhibitors and potential for cancer polypharmacology.
abstract: A series of anthra[1,2-d]imidazole-6,11-dione derivatives were synthesized and evaluated for telomerase inhibition, hTERT expression and suppression of cancer cell growth in vitro. All of the compounds tested, except for compounds 4, 7, 16, 24, 27 and 28 were selected by the NCI screening system. Among them, compounds 16, 39, and 40 repressed hTERT expression without greatly affecting cell growth, suggesting for the selectivity toward hTERT expression. Taken together, our findings indicated that the analysis of cytotoxicity and telomerase inhibition might provide information applicable for further developing potential telomerase and polypharmacological targeting strategy.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Tsung-Chih
authors.initials: TC
authors.lastname: Chen
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Lee
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsieh
authors.forename: Fong-Chun
authors.initials: FC
authors.lastname: Huang
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Huang
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
authors.forename: Jing-Jer
authors.initials: JJ
authors.lastname: Lin
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C509186:TERT protein, human; D019098:Telomerase