title: Synthesis, antiproliferative activities and telomerase inhibition evaluation of novel asymmetrical 1,2-disubstituted amidoanthraquinone derivatives.
abstract: A series of diversely asymmetrical mono- or disubstituted 1,2-diamidoanthraquinone derivatives were synthesized and evaluated for drug-induced cytotoxicity by SRB assay, telomerase inhibitory activity by TRAP assay, and hTERT expression by SEAP assay. Interestingly, compounds 4, 11, 21, 32 and 36 exhibited selective potent antiproliferative activities by NCI with IC(50) values in the micromolar range. Of these, only compound 8 showed an IC(50) value of 0.95 μM against PC-3 cell lines (human prostate cancer) by SRB assay. All the synthesized compounds exhibited a poor or modest telomerase inhibitory activity by TRAP assay suggesting another mode of action for these compounds. Compound 11 showed broad inhibition against different types of cancer cell lines in the micromolar and submicromolar range.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Lee
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Huang
authors.forename: Pen-Yuan
authors.initials: PY
authors.lastname: Lin
authors.forename: Fong-Chun
authors.initials: FC
authors.lastname: Huang
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: Tsung-Chih
authors.initials: TC
authors.lastname: Chen
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: D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D004791:Enzyme Inhibitors; D019098:Telomerase