title: Synthesis, telomerase evaluation and anti-proliferative studies on various series of diaminoanthraquinone-linked aminoacyl residue derivatives.
abstract: Four series of compounds containing an anthraquinone-linked moiety and symmetrical or asymmetrical aminoacyl residues in side chains at positions 1,4-, 1,5-, 2,6-, and 2,7- were synthesized and evaluated for their inhibitory effects toward telomerase and hTERT expression. Of these, only compound B11 showed selective inhibition of telomerase activity. Although it is not as competent as several of the anthraquinones we identified previously, nevertheless, the result is consistent with that the general structure moiety at the 1,5-position of diaminoanthraquinone-linked compound is important for the telomerase inhibitory activity. Interestingly, compounds A6, A8, C8, and D8 exhibited selective repressing activities toward hTERT expression and showed less effect toward proliferation of the treated cancer cells. Although it is not apparent which structure moiety is responsible for the telomerase repression effects of these compounds, they could be further developed as potential anti-tumor agents.
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Fong-Chun
authors.initials: FC
authors.lastname: Huang
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Huang
authors.forename: Ruey-Hui
authors.initials: RH
authors.lastname: Chen
authors.forename: Jia-Er
authors.initials: JE
authors.lastname: Wu
authors.forename: Tsung-Chih
authors.initials: TC
authors.lastname: Chen
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: Chia-Chung
authors.initials: CC
authors.lastname: Lee
authors.forename: Jin-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Jing-Jer
authors.initials: JJ
authors.lastname: Lin
authors.forename: Hsu-Shan
authors.initials: HS
authors.lastname: Huang
mesh_terms: D000215:Acylation; D000586:Amination; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; C509186:TERT protein, human; D019098:Telomerase