Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis

John R. Goodell, Andrei V. Ougolkov, Hiroshi Hiasa, Harneet Kaur, Rory P Remmel, Daniel D. Billadeau, David M Ferguson

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)179-182
Number of pages4
JournalJournal of Medicinal Chemistry
Volume51
Issue number2
DOIs
StatePublished - Jan 24 2008

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Acridines
Type II DNA Topoisomerase
Pancreatic Neoplasms
Aminacrine
Cell Proliferation
Apoptosis
Enzyme Induction
DNA
G1 Phase
S Phase
Cell Death
Pharmaceutical Preparations

Cite this

Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis. / Goodell, John R.; Ougolkov, Andrei V.; Hiasa, Hiroshi; Kaur, Harneet; Remmel, Rory P; Billadeau, Daniel D.; Ferguson, David M.

In: Journal of Medicinal Chemistry, Vol. 51, No. 2, 24.01.2008, p. 179-182.

Research output: Contribution to journalArticle

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AU - Billadeau, Daniel D.

AU - Ferguson, David M

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