Human telomerase inhibition by substituted acridine derivatives.
A series of 3,6-disubstituted acridine derivatives have been rationally designed as telomerase inhibitors. They have been designed on the basis that inhibition of telomerase occurs by stabilising G-quadruplex structures formed by the folding of telomeric DNA. The most potent inhibitors have IC50 values against telomerase of between 1.3 and 8 microM, comparable to their cytotoxicity in ovarian cancer cell lines.
Harrison
R J
RJ
CRC Biomolecular Structure Unit, The Institute of Cancer Research, Sutton, Surrey, UK.
Gowan
S M
SM
Kelland
L R
LR
Neidle
S
S
D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000166:Acridines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019098:Telomerase