Acridine-Based Agents with Topoisomerase II Activity Inhibit Pancreatic Cancer Cell Proliferation and Induce Apoptosis
Journal of Medicinal Chemistry2007Vol. 51(2), pp. 179–182
Citations Over TimeTop 18% of 2007 papers
John R. Goodell, Andrei V. Ougolkov, Hiroshi Hiasa, Harneet Kaur, Rory P. Remmel, Daniel D. Billadeau, David M. Ferguson
Abstract
A series of substituted 9-aminoacridines is evaluated for antiproliferative activity toward pancreatic cancer cells. The results indicate that the compounds inhibit cell proliferation by inducing a G1-S phase arrest. A model is also developed that explains the molecular basis to inhibition through a DNA "threading" mechanism. We conclude that the drug-DNA complex formed blocks topoisomerase II binding and activity leading to catalytic inhibition of the enzyme and the induction of apoptosis and programmed cell death.
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