Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles

Journal of Medicinal Chemistry

Volumn 49, Issue 21, 2006, Pages 6283-6289

  Nagarajan, Muthukaman ^a   Morrell, Andrew ^a   Ioanoviciu, Alexandra ^a   Antony, Smitha ^b   Kohlhagen, Glenda ^b   Agama, Keli ^b   Hollingshead, Melinda ^c   Pommier, Yves ^b   Cushman, Mark ^a  

^a PURDUE UNIVERSITY   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; DNA TOPOISOMERASE; DNA TOPOISOMERASE INHIBITOR; HETEROCYCLIC COMPOUND; INDENOISOQUINOLONE DERIVATIVE; LACTAM DERIVATIVE; NITROGEN; UNCLASSIFIED DRUG;

ARTICLE; BASE PAIRING; BIOLOGICAL ACTIVITY; CANCER CELL; COMPLEX FORMATION; CYTOTOXICITY; DRUG ACTIVITY; DRUG DNA INTERACTION; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME INHIBITOR COMPLEX; HUMAN; HUMAN CELL; MOLECULAR INTERACTION; MOLECULAR MODEL; PHARMACOPHORE;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DNA TOPOISOMERASES, TYPE I; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; IMIDAZOLES; INDENES; ISOQUINOLINES; LACTAMS; MODELS, MOLECULAR; MORPHOLINES; PIPERAZINES; PIPERIDINES; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP; TOPOISOMERASE I INHIBITORS; TRIAZOLES;

EID: 33750142705     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060564z     Document Type: Article

References (22)

1. Paull, K. D.; Hamel, E.; Malspeis, L. Prediction of Biochemical Mechanism of Action from the In Vitro Antitumor Screen of the National Cancer Institute. Cancer Chemotherapeutic Agents; American Chemical Society: Washington, DC, 1995; pp 9-45.
2. Kohlhagen, G.; Paull, K.; Cushman, M.; Nagafuji, P.; Pommier, Y. Protein-Linked DNA Strand Breaks Induced by NSC 314622, a Novel Noncamptothecin Topoisomerase I Poison. Mol. Pharmacol. 1998, 54 50-58.
3. Ioanoviciu, A.; Antony, S.; Pommier, Y.; Staker, B. L.; Stewart, L.; Cushman, M. Synthesis and Mechanism of Action Studies of a Series of Norindenoisoquinoline Topoisomerase I Poisons Reveal an Inhibitor with a Flipped Orientation in the Ternary DNA-Enzyme-Inhibitor Complex As Determined by X-ray Crystallographic Analysis. J. Med. Chem. 2005, 48, 4803-4814.
4. Morrell, A.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Synthesis of Nitrated Indenoisoquinolines as Topoisomerase I Inhibitors. Bioorg. Med. Chem. Lett. 2004, 14, 3659-3663.
5. Nagarajan, M.; Morrell, A.; Fort, B. C.; Meckley, M. R.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Synthesis and Anticancer Activity of Simplified Indenoisoquinoline Topoisomerase I Inhibitors Lacking Substituents on the Aromatic Rings. J. Med. Chem. 2004, 47, 5651-5661.
6. Xiao, X.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Design, Synthesis, and Biological Evaluation of Cytotoxic 11- Aminoalkenylindenoisoquinoline and 11-Diaminoalkenylindenoisoquinoline Topoisomerase 1 Inhibitors. Bioorg. Med. Chem. 2004, 12, 5147-5160.
7. Nagarajan, M.; Xiao, X.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Design, Synthesis, and Biological Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Featuring Polyamine Side Chains on the Lactam Nitrogen. J. Med. Chem. 2003, 46, 5712-5724.
8. Fox, B. M.; Xiao, X.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Staker, B.; Stewart, L.; Cushman, M. Design, Synthesis, and Biological Evaluation of Cytotoxic 11-Alkenylindenoisoquinoline Topoisomerase I Inhibitors and Indenoisoquinoline-Camptothecin Hybrids. J. Med. Chem. 2003, 46, 3275-3282.
9. Morrell, A.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Synthesis of Benz[d]indeno[1,2-b]pyran-5,11-diones: Versatile Intermediates for the Design and Synthesis of Topoisomerase I Inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 1846-1849.
10. Pommier, Y. Eukaryotic DNA Topoisomerase I: Genome Gate Keeper and Its Intruders, Camptothecins. Semin. Oncol. 1996, 23, 1-10.
11. (a) Jaxel, C.; Kohn, K. W.; Wani, M. C.; Pommier, Y. Structure-Reactivity Study of the Actions of Camptothecin Derivatives on Mammalian Topoisomerase I: Evidence for a Specific Receptor Site and a Relation to Antitumor Activity. Cancer. Res. 1989, 49, 1465-1469.
12. (b) Minami, H.; Beijnen, J. H.; Verweij, J.; Ratain, M. J. Limited Sampling Model for the Area under the Concentration Time Curve of Total Topotecan. Clin. Cancer Res. 1996, 2, 43-46.
13. (c) Danks, M. K.; Pawlik, C. A.; Whipple, D. O.; Wolverton, J. S. Intermittant Exposure of Medulloblastoma Cells to Topotecan Produces Growth Inhibition equivalent to Continuous Exposure. Curr. Top. Med. Chem. 1997, 3, 1731-1738.
14. (d) Haas, N. B.; LaCreta, F. P.; Walczak, J.; Hudes, G. R.; Brennan, J. M.; Ozols, R. F.; O'Dwyer, P. J. Phasel/Pharmaco-kinetic Study of Topotecan by 24-Hour Continuous Infusion Weekly. Cancer Res. 1994, 54, 1220-1226.
15. Antony, S.; Kohlhagen, G.; Agama, K.; Jayaraman, M.; Cao, S.; Durrani, F.; Rustum, Y.; Cushman, M.; Pommier, Y. Cellular Topoisomerase 1 Inhibition and Antiproliferative Activity by MJ-III-65 (NSC 706744), an Indenoisoquinoline Topoisomerase I Poison. Mol. Pharmacol. 2005, 67, 523-530.
16. Meng, L. H.; Liao, Z. Y.; Pommier, Y. Non-Camptothecin DNA Topoisomerase I Inhibitors in Cancer Therapy. Curr. Top. Med. Chem. 2003, 3, 305-320.
17. Staker, B. L.; Hjerrild, K.; Feese, M. D.; Behnke, C. A.; Burgin, A. B., Jr.; Stewart, L. The Mechanism of Topoisomerase I Poisoning by a Camptothecin Analogue. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15387-15392.
18. Staker, B. L.; Feese, M. D.; Cushman, M.; Pommier, Y.; Zembower, D.; Stewart, L.; Burgin, A. B. Structures of Three Classes of Anticancer Agents Bound to the Human Topoisomerase I-DNA Covalent Complex. J. Med. Chem. 2005, 48, 2336-2345.
19. Marchand, C.; Antony, S.; Kohn, K. W.; Cushman, M.; Ioanoviciu, A.; Staker, B. L.; Burgin, A. B.; Stewart, L.; Pommier, Y. A Novel Norindenoisoquinoline Structure Reveals a Common Interfacial Inhibitor Paradigm for Ternary Trapping of the Topoisomerase I-DNA Covalent Complex. Mol. Cancer Ther. 2006, 5, 287-295.
20. Cushman, M.; Jayaraman, M.; Vroman, J. A.; Fukunaga, A. K.; Fox, B. M.; Kohlhagen, G.; Strumberg, D.; Pommier, Y. Synthesis of New Indeno[1,2-c] isoquinolines: Cytotoxic Non-Camptothecin Topoisomerase I Inhibitors. J. Med. Chem. 2000, 43, 3688-3698.
21. Hollingshead, M.; Plowman, J.; Alley, M.; Mayo, J.; Sausville, E. The Hollow Fiber Assay. Contrib. Oncol. 1999, 54, 109-120.
22. Pourquier, P.; Ueng, L.-M.; Fertala, J.; Wang, D.; Park, H.-J.; Essigman, J.; Bjornsti, M.-A.; Pommier, Y. Induction of Reversible Complexes between Eukaryotic DNA Topoisomerase I and DNA-Containing Oxidative Base Damages. 7,8-Dihydro-8-Oxoguanine and 5-Hydroxycytosine. J. Biol. Chem. 1999, 274, 8516-8523.