A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor

Journal of Medicinal Chemistry

Volumn 49, Issue 26, 2006, Pages 7740-7753

  Morrell, Andrew ^a   Antony, Smitha ^b   Kohlhagen, Glenda ^b   Pommier, Yves ^b   Cushman, Mark ^a  

^a PURDUE UNIVERSITY   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (3 AMINOPROPYL) 5,6 DIHYDRO 7 METHOXY 3 NITRO 5,11 DIOXO 11H INDENO[1,2 C]ISOQUINOLINE; 6 (3 AMINOPROPYL) 5,6 DIHYDRO 9 METHOXY 3 NITRO 5,11 DIOXO 11H INDENO[1,2 C]ISOQUINOLINE; 6 (3 AZIDOPROPYL) 5,6 DIHYDRO 9 METHOXY 3 NITRO 5,11 DIOXO 11H INDENO[1,2 C]ISOQUINOLINE; 6 (3 CHLOROPROPYL) 5,6 DIHYDRO 9 METHOXY 3 NITRO 5,11 DIOXO 11H INDENO[1,2 C]ISOQUINOLINE; CAMPTOTHECIN; DNA TOPOISOMERASE INHIBITOR; ISOQUINOLINE DERIVATIVE; MJ III 65; UNCLASSIFIED DRUG;

ARTICLE; BASE PAIRING; BIOLOGICAL ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; NITRATION; NONHUMAN; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; DNA; DNA TOPOISOMERASES, TYPE I; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; INDENES; ISOQUINOLINES; MODELS, MOLECULAR; NITRATES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33845955224     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060974n     Document Type: Article

References (37)

1. Kohlhagen, G.; Paull, K. D.; Cushman, M.; Nagafuji, P.; Pommier, Y. Protein-Linked DNA Strand Breaks Induced by NSC 314622, a Novel Noncamptothecin Topoisomerase I Poison. Mol. Pharmacol. 1988, 54, 50-58.
2. Antony, S.; Jayaraman, M.; Laco, G.; Kohlhagen, G.; Kohn, K. W.; Cushman, M.; Pommier, Y. Differential Induction of Topoisomerase I-DNA Cleavage Complexes by the Indenoisoquinoline MJ-III-65 (NSC 706744) and Camptothecin: Base Sequence Analysis and Activity against Camptothecin-Resistant Topoisomerase I. Cancer Res. 2003, 63, 7428-7435.
3. Antony, S.; Kohlhagen, G.; Agama, K.; Jayaraman, M.; Cao, S.; Durrani, F. A.; Rustum, Y. M.; Cushman, M.; Pommier, Y. Cellular Topoisomerase I Inhibition and Antiproliferative Activity by MJ-III-65 (NSC 706744), an Indenoisoquinoline Topoisomerase I Poison. Mol. Pharmacol. 2005, 67, 523-530.
4. Wall, M. E.; Wani, M. C.; Cook, C. E.; Palmer, K. H.; McPhall, A. T.; Sim, G. A. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 1966, 88, 3888-3890.
5. Hsiang, Y. H.; Hertzberg, R.; Hecht, S.; Liu, L. F. Camptothecin Induces Protein-Linked DNA Breaks via Mammalian DNA Topoisomerase 1. J. Biol. Chem. 1985, 260, 14873-14878.
6. Nitiss, J. L.; Wang, J. C. DNA Topoisomerase-Targeting Antitumor Drugs Can Be Studied in Yeast. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 7501-7505.
7. Bjornski, M. A.; Benedetti, P.; Viglianti, G. A.; Wang, J. C. Expression of Human DNA Topoisomerase I in Yeast Cells Lacking Yeast DNA Topoisomerase I: Restoration of Sensitivity of the Cells to the Antitumor Drug Camptothecin. Cancer Res. 1989, 49, 6318-6323.
8. Pommier, Y.; Kohlhagen, G.; Kohn, K. W.; Leteurtre, F.; Wani, M. C.; Wall, M. E. Interaction of an Alkylating Camptothecin Derivative with a DNA Base at Topoisomerase I-DNA Cleavage Sites. Proc. Natl. Acad Aci. U.S.A. 1995, 92, 8861-8865.
9. Pommier, Y.; Pourquier, P.; Fan, Y.; Strumberg, D. Mechanism of Action of Eukaryotic DNA Topoisomerase I and Drugs Targeted to the Enzyme. Biochem. Biophys. Acta 1998, 1400, 83-106.
10. 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 Analog. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15387-15392.
11. 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.
12. 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.
13. 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.
14. Chen, A. Y.; Liu, L. F. DNA Topoisomerases: Essential Enzymes and Lethal Targets. Rev. Pharmacol. Toxicol. 1994, 34, 191-218.
15. Strumberg, D.; Pommier, Y.; Paull, K.; Jayaraman, M.; Nagafuji, P.; Cushman, M. Synthesis of Cytotoxic Indenoisoquinoline Topoisomerase I Poisons. J. Med. Chem. 1999, 42, 446-457.
16. 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.
17. Jayaraman, M.; Fox, B. M.; Hollingshead, M.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Synthesis of New Dihydroindeno[1,2-c]isoquinoline and Indenoisoquinolinium Chloride Topoisomerase I Inhibitors Having High in Vivo Anticancer Acitivity in the Hollow Fiber Animal Model. J. Med. Chem. 2002, 45, 242-249.
18. Fox, B. M.; Xiao, X.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Staker, B. L.; 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.
19. 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.
20. 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.
21. Xiao, X.; Antony, S.; Kohlhagen, G.; Pommier, Y.; Cushman, M. Design, Synthesis, and Biological Evaluation of Cytotoxic 11- Aminoalkenylindenoisoquinoline and 11-Diaminoalkenylindenoisoquinoline Topoisomerase I Inhibitors. Bioorg. Med. Chem. 2004, 12, 5147-5160.
22. 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.
23. Cushman, M.; Cheng, L. Stereoselective Oxidation by Thionyl Chloride Leading to the Indeno[1,2-c]isoquinoline System. J. Org. Chem. 1978, 43, 3781-3783.
24. 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.
25. Xiao, X.; Cushman, M. An Ab Initio Quantum Mechanics Calculation that Correlates with Ligand Orientation and DNA Cleavage Site Selectivity in Camptothecin-DNA-Topoisomerase I Ternary Cleavage Complexes. J. Am. Chem. Soc. 2005, 127, 9960-9961.
26. Xiao, X.; Cushman, M. Effect of E-Ring Modifications in Camptothecin on Topoisomerase I Inhibition: A Quantum Mechanics Treatment. J. Org. Chem. 2005, 70, 9584-9587.
27. Xiao, X.; Antony, S.; Pommier, Y.; Cushman, M. On the Binding of Indeno[1,2-c]isoquinolines in the DNA-Topoisomerase I Cleavage Complex. J. Med. Chem. 2005, 48, 3231-3238.
28. Singh, S. K.; Ruchelman, A. L.; Li, T.-K.; Liu, A.; Liu, L. F.; LaVoie, E. J. Nitro and Amino Substitution in the D-Ring of 5-(2-Dimethylaminoethyl)-2, 3-methylenedioxy-5H-dibenzo[c,h][1,6]napthyridin-6-ones: Effect on Topoisomerase-1 Targeting Activity and Cytotoxicity. J. Med. Chem. 2003, 46, 2254-2257.
29. Whitmore, W. F.; Cooney, R. C. The Preparation of Homophthalyl Cyclic hydrazide and 4-Aminohomophthalyl Cyclic Hydrazide. J. Am. Chem. Soc. 1944, 66, 1237-1240.
30. Negi, A. S.; Chattopadhyay, S. K.; Srivastava, S.; Bhattacharya, A. K. A Simple Regioselective Demethylation of p-Aryl Methyl Ethers Using Aluminum Chloride-Dichloromethane System. Synth. Commun. 2005, 35, 15-21.
31. Sudo, Y.; Arai, S.; Nishida, A. Facile and Regioselective Dealkylation of Alkyl Aryl Ethers Using Niobium(V) Pentachloride. Eur. J. Org. Chem. 2006, 3, 752-758.
32. Xiao, X.; Miao, Z. H.; Antony, S.; Pommier, Y.; Cushman, M. Dihydroindenoisoquinolines Function as Prodrugs of Indenoisoquinolines. Bioorg. Med. Chem. Lett. 2005, 15, 2795-2798.
33. Morrell, A.; Jayaraman, M.; Nagarajan, M.; Fox, B. M.; Meckley, M. R.; Ioanoviciu, A.; Pommier, Y.; Antony, S.; Hollingshead, M.; Cushman, M. Evaluation of Indenoisoquinoline Topoisomerase I Inhibitors Using a Hollow Fiber Assay. Bioorg. Med. Chem. Lett. 2006, 16, 4395-4399.
34. Jaxel, C.; Kohn, K. W.; Wani, M. C.; Wall, M. E.; Pommier, Y. Structure-Activity Study of the Actions of Camptothecin Derivatives on Mammalian Topoisomerase 1: Evidence for a Specific Receptor Site and a Relation to Antitumor Activity. Cancer Res. 1989, 49, 1465-1469.
35. Fan, Y.; Weinstein, J. N.; Kohn, K. W.; Shi, L. M.; Pommier, Y. Molecular Modeling Studies of the DNA-Topoisomerase I Ternary Cleavable Complex with Camptothecin. J. Med. Chem. 1998, 41, 2216-2226.
36. Yus, M.; Soler, T.; Foubelo, F. A New and Direct Synthesis of 2-Substituted Pyrrolidines. J. Org. Chem. 2001, 66, 6207-6208.
37. Pourquier, P.; Ueng, L.-M.; Fertala, J.; Wang, D.; Park, H.-K.; Essigmann, J. M.; 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.