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.

Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion

“…A number of large interstitial deletions have been identified, some of which can be linked to ERG-positive (including for example deletions at 3p13 and the PTEN locus at 10q23), or ERG-negative cancers (for example deletions at 5q21, 6q15 or 2q23) (21,(25)(26)(27)31,42,43). Likewise, balanced as well as imbalanced translocations have been detected in both ERG-positive and ERG-negative tumors (29,20).…”

Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents

“…Details of the methodology are described in our previous reports [21,24,25,[32][33][34][35][36]. There are two stages of the screening process that starts with the evaluation of the test compounds against the 60 human tumor cell lines at a single dose of 10 µM.…”