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 Remmel; Daniel D. Billadeau; David M. Ferguson

doi:10.1021/jm701228e

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 Remmel, Daniel D. Billadeau, David M. Ferguson

Oncology

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

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 language	English (US)
Pages (from-to)	179-182
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	2
DOIs	https://doi.org/10.1021/jm701228e
State	Published - Jan 24 2008

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm701228e

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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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AU - Goodell, John R.

AU - Ougolkov, Andrei V.

AU - Hiasa, Hiroshi

AU - Kaur, Harneet

AU - Remmel, Rory

AU - Billadeau, Daniel D.

AU - Ferguson, David M.

PY - 2008/1/24

Y1 - 2008/1/24

N2 - 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.

AB - 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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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

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

Abstract

ASJC Scopus subject areas

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