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

Journal of Medicinal Chemistry

Volumn 51, Issue 2, 2008, Pages 179-182

  Goodell, John R ^a   Ougolkov, Andrei V ^c   Hiasa, Hiroshi ^b   Kaur, Harneet ^a   Remmel, Rory ^a   Billadeau, Daniel D ^c   Ferguson, David M ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c Mayo Clinic   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOACRIDINE DERIVATIVE; DIMETHYL SULFOXIDE; DNA TOPOISOMERASE (ATP HYDROLYSING); GYRASE INHIBITOR; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CONTROLLED STUDY; DRUG DNA INTERACTION; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; PANCREAS CANCER;

AMINOACRIDINES; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; DNA; DNA TOPOISOMERASES, TYPE II; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MODELS, MOLECULAR; PANCREATIC NEOPLASMS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 38349194792     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701228e     Document Type: Article

References (17)

1. Denny, W. A. Chemotherapeutic effects of acridine derivatives. Med. Chem. Rev. - Online 2004, 1, 257-266.
2. Denny, W. A.; Baguley, B. C. Dual topoisomerase I/II inhibitors in cancer therapy. Curr. Top. Med. Chem. 2003, 3, 339-353.
3. Walker, J. V.; Nitiss, J. L. DNA topoisomerase II as a target for cancer chemotherapy. Cancer Invest. 2002, 20, 570-589.
4. Burden, D. A.; Osheroff, N. Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme. Biochim. Biophys. Acta 1998, 1400, 139-154.
5. Holden, J. A. DNA topoisomerases as anticancer drug targets: from the laboratory to the clinic. Curr. Med. Chem.: Anti-Cancer Agents 2001, 1, 1-25.
6. Larsen, A. K.; Escargueil, A. E.; Skladanowski, A. Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol. Ther. 2003, 99, 167-181.
7. Goodell, J. R.; Madhok, A. A.; Hiasa, H.; Ferguson, D. M. Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity. Bioorg. Med. Chem. 2006, 14, 5467-5480.
8. Kaufmann, S. H. Cell death induced by topoisomerase-targeted drugs: more questions than answers. Biochim. Biophys. Acta 1998, 1400, 195-211.
9. Dartsch, D. C.; Schaefer, A.; Boldt, S.; Kloch, W.; Marquardt, H. Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis. Apoptosis 2002, 7, 537-548.
10. Yang, D.; Wang, A. H.-J. Structure by NMR of antitumor drugs aclacinomycin A and B complexed to d(CGTACG). Biochemistry 1994, 33, 6595-6604.
11. Todd, A. K.; Adams, A.; Thorpe, J. H.; Denny, W. A.; Wakelin, L. P.; Cardin, C. J. Major groove binding and "DNA-induced" fit in the intercalation of a derivative of the mixed topoisomerase I/II poison N-(2-(dimethylamino)ethyl)acridine-4-carboxamide (DACA) into DNA: X-ray structure complexed to d(CG(5-BrU)ACG)2 at 1.3-.ANG. Resolution. J. Med. Chem. 1999, 42, 536-540.
12. Adams, A. Crystal structures of acridines complexed with nucleic acids. Curr. Med. Chem. 2002, 9, 1667-1675.
13. Schrodinger, Inc., 120 West 45th Street, 32nd Floor, New York, NY 10036-4041.
14. Wakelin, L. P.; Chetcuti, P.; Denny, W. A. Kinetic and equilibrium binding studies of amsacrine-4-carboxamides: a class of asymmetrical DNA intercalating agents which bind by threading through the DNA helix. J. Med. Chem. 1990, 33, 2039-2044.
15. Crenshaw, J. M.; Graves, D. E.; Denny, W. A. Interactions of acridine antitumor agents with DNA: binding energies and groove preferences. Biochemistry 1995, 34, 13682-13687.
16. Krishnamurthy, M.; Gooch, B. D.; Beal, P. A. RNA binding and thiolytic stability of a quinoline-containing helix-threading peptide. Org. Biomol. Chem. 2006, 4, 639-645 .
17. Oppegard, L. M.; Goodell, J. R.; Kaur, H.; Billadeau, D. D.; Ferguson. D. M.; Hiasa, H. Novel acridine-based compounds with anti-pancreatic cancer activity intercalate into DNA and inhibit the catalytic activity of human topoisomerase II. Biochemistry,to be submitted.