A novel inhibitor of human telomerase derived from 10H-indolo[3,2-b]quinoline.
The bis-dimethylaminoethyl derivative of quindoline (10H-indolo[3,2-b]quinoline), an alkaloid from the West African shrub Cryptolepis sanguinolenta, has been synthesised. This has been shown to have modest cytotoxicity, as well as inhibitory activity against the telomerase enzyme. It is hypothesised that the latter activity is due to stabilisation of an intermediate guanine-quadruplex complex, in accordance with computer modelling.
Caprio
V
V
Chemistry Department, Reading University, Whiteknights, UK.
Guyen
B
B
Opoku-Boahen
Y
Y
Mann
J
J
Gowan
S M
SM
Kelland
L M
LM
Read
M A
MA
Neidle
S
S
D000634:Aminoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C092774:10H-indolo(3,2-b)quinolin-11-ylamine; D000634:Aminoquinolines; D000970:Antineoplastic Agents; D007211:Indoles; D011804:Quinolines; D018894:Reverse Transcriptase Inhibitors; D019098:Telomerase