5-[ω-aminoalkyl)amino]-4-[N-(ω-aminoalkyl)carbamoyl]-9-ox-9,10- dihydroacridines as intercalating cytotoxic agents: Synthesis, DNA binding, and biological evaluation

Journal of Medicinal Chemistry

Volumn 40, Issue 23, 1997, Pages 3749-3755

  Antonini, Ippolito ^a   Polucci, Paolo ^a   Jenkins, Terence C ^b   Kelland, Lloyd R ^b   Menta, Ernesto ^c   Pescalli, Nicoletta ^c   Stefanska, Barbara ^d   Mazerski, Jan ^d   Martelli, Sante ^a  

^a UNIVERSITY OF CAMERINO   (Italy)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c Boehringer Ingelheim Italia SpA   (Italy)

^d GDANSK UNIVERSITY OF TECHNOLOGY   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

1 [[2 (DIMETHYLAMINO)ETHYL]AMINO] 4 [N [2 (DIMETHYLAMINO)ETHYL]CARBAMOYL] 9 OXO 9,10 DIHYDROACRIDINE; ACRIDAN DERIVATIVE; ANTINEOPLASTIC AGENT; INTERCALATING AGENT; UNCLASSIFIED DRUG; ACRIDINE DERIVATIVE; DNA;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER; CANCER CELL CULTURE; COLON CARCINOMA; DNA BINDING; DRUG CYTOTOXICITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LEUKEMIA L 1210; MELANOMA CELL; MOUSE; NONHUMAN; OVARY CARCINOMA; PARTITION COEFFICIENT; ANIMAL; CATTLE; CELL CULTURE; DNA DENATURATION; DRUG EFFECT; DRUG SCREENING; METABOLISM; SPECTROFLUOROMETRY; SYNTHESIS;

ACRIDINES; ANIMALS; ANTINEOPLASTIC AGENTS; CATTLE; DNA; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INTERCALATING AGENTS; MICE; NUCLEIC ACID DENATURATION; SPECTROMETRY, FLUORESCENCE; TUMOR CELLS, CULTURED;

EID: 0030613528     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970114u     Document Type: Article

References (36)

1. (a) Showalter, H. D. H.; Johnson, J. L.; Werbel, L. M.; Leopold, W. R.; Jackson, R. C.; Elslager, E. F. 5-[(Aminoalkybamino]-substituted Anthra[1,9-cdlpyrazol-6(2H)-ones as Novel Anticancer Agents. Synthesis and Biological Evaluation. J. Med. Chem. 1984, 27, 253-255.
2. (b) Leopold, W. R.; Nelson, J. M.; Plowman, J.; Jackson, R. C. Anthrapyrazoles. A New Class of Intercalating Agents with High Level, Broad Spectrum Activity Against Murine Tumors. Cancer Res. 1985, 45, 5532-5539.
3. (a) Capps, D. B.; Kesten, S. R.; Shillis, J.; Plowman, J. 2-Aminoalkyl-5-mtropyrazolo[3,4,5-kl]acridines, a New Class of Anticancer Agents. Proc. Am. Assoc. Cancer Res. 1986, 27, 277.
4. (b) LoRusso, P.; Wozniak, J.; Polin, L.; Capps, D.; Leopold, W. R.; Werbel, L. M.; Biernat, L.; Dan, M. E.; Corbett, T. H. Antitumor Efficacy of PD 115934 (NSC 366140) Against Solid Tumors of Mice. Cancer Res. 1990, 60, 4900-4905.
5. (c) Capps, D. B.; Dunbar, J.; Kesten, S. R.; Shilhs, J.; Werbel, L. M.; Plowman, J.; Ward, D. L. 2-(Ammoalkyl)-5-nitropyrazolo[3,4,5-kl]acridines, a New Class of Anticancer Agents. J. Med. Chem. 1992, 35, 4770-4778.
6. (a) Atwell, G. J.; Rewcastle, G. W.; Baguley, B. C.; Denny, W. A. Potential Antitumor Agents. 50. In Vivo Solid Tumor Activity of N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide. J. Med. Chem. 1987, 30, 664-669.
7. (b) Haldane, A.; Finlay, G. J.; Baguley, B. C. Unusual Dynamics of Killing of Cultured Lewis Lung Cells by the DNA-intercalating Antitumor Agent N-[2-(Dimethylamino)ethyI]acridine-4-carboxamide. Cancer Chemother. Pharmacol. 1992, 29, 474-479.
8. (a) Zee-Cheng, R. K Y.; Cheng, C. C. Antineoplastic Agents. Structure-Activity Relationship Study of Bis(substituted aminoalkylamino)anthraquinones. J. Med. Chem. 1978, 21, 291-294.
9. (b) Zee-Cheng, R. K. Y.; Podrebarac, E. G.; Menon, C. S.; Cheng, C. C. Structural Modification Study of Bis(substituted aminoalkylamino)anthraquinones. An Evaluation of the Relationship of the [2-[(2-Hydroxyethyl)amino]ethyl]amino Side Chain with Antineoplastic Activity. J. Med. Chem. 1979, 22, 501-505.
10. (c) Murdock, K. C.; Child, R. G.; Fabio, P. F.; Angier, R. B.; Wallace, R. E.; Durr, F. E.; Citarella, R. V. Antitumor Agents. 1. 1,4-Bis[(aminoalkyl)anuno]-9,10-anthracenediones. J. Med. Chem. 1979, 22, 1024-1030.
11. Krapcho, A. P.; Petry, M. E.; Getahun, Z.; Landi, J. J.; Stallman, J.; Polsenberg, J. F.; Gallagher, C. E.; Maresch, M. J.; Hacker, M. P.; Giuliani, F. G.; Beggolin, G.; Pezzoni, G.; Menta, E.; Manzotti, C.; Oliva, A.; Spinelli, S.; Tognella, S. 6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A Novel Class of Chromophore-modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluation. J. Med. Chem. 1994, 37, 828-837.
12. Antonini, I.; Cola, D.; Polucci, P.; Bontemps-Gracz, M.; Borowski, E.; Martelli, S. Synthesis of (Dialkylamino)alkyl-disubstituted Pyrimido[5,6,l-efe]acridines, a Novel Group of Anticancer Agents Active on a Multidrug Resistant Cell Line. J. Med. Chem. 1995, 38, 3282-3286.
13. Antonini, I.; Cola, D.; Martelli, S.; Cholody, W. M.; Konopa, J. Pyrimidoacridine Derivatives as Potential Antitumor Agents. Farmaco 1992, 47, 1035-1046.
14. (a) Palmer, B. D.; Rewcastle, G. W.; Atwell, G. J.; Baguley, B. C.; Denny, W. A. Potential Antitumor Agents. 54. Chromophore Requirements for in Vivo Antitumor Activity among the General Class of Linear Tricyclic Carboxamides, J. Med. Chem. 1988, 31, 707-712.
15. (b) Chen, Q.; Deady, L. W.; Baguley, B. C.; Denny, W. A. Electron-deficient DNA-intercalating Agents as Antitumor Drugs: Aza Analogues of the Experimental Clinical Agent N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide. J. Med. Chem. 1994, 37, 593-597.
16. Rewcastle, G. W.; Denny, W. A. The Synthesis of Substituted 9-Oxoacridan-4-carboxylic Acids; Part 3. The Reaction of Methyl Anthranilates with Diphenyliodonium-2-carboxylates. Synthesis 1985, 220-222.
17. Antonini, I.; Polucci, P.; Cola, D.; Palmieri, G. F.; Martelli, S. Synthesis of 7-Oxo-7H-benzo[e]perimidine-4-carboxamides as Potential Antitumor Drugs. Farmaco 1992, 47, 1385-1393.
18. McConnaughie, A. W.; Jenkins, T. C. Novel Acridine-Triazenes as Prototype Combilexins: Synthesis, DNA Binding, and Biological Activity. J. Med. Chem. 1995, 38, 3488-3501.
19. (a) Morgan, A. R.; Lee, J. S.; Pulleyblank, D. E.; Murray, N. L.; Evans, D. H. Review: Ethidium Fluorescence Assays. Part 1. Physicochemical Studies. Nucleic Acids Res. 1979, 7, 547-569.
20. (b) Baguley, B. C.; Denny, W. A.; Atwell, G. J.; Cain, B. F. Potential Antitumor Agents. 34. Quantitative Relationships between DNA Binding and Molecular Structure for 9-Anilinoacridines Substituted in the Anilino Ring. J. Med. Chem. 1981, 24, 170-177.
21. Baguley, B. C. Nonintercalative DNA-Binding Antitumour Compounds. Mol. Cell Biochem. 1982, 43, 167-181.
22. Bailly, C.; Pommery, N.; Houssin, R.; Hénichart, J.-P. Design, Synthesis, DNA Binding, and Biological Activity of a Series of DNA Minor Groove-Binding Intercalating Drugs. J. Pharm. Sci. 1989, 78, 910-917.
23. (a) Brown, D. G.; Sanderson, M. R.; Skelly, J. V.; Jenkins, T. C.; Brown, T.; Garman, E.; Stuart, D. I.; Neidle, S. Crystal Structure of a Berenil-Oligonucleotide Complex: The Role of Water in Sequence-Specific Ligand Binding. EMBO J. 1990, 9, 1329-1334,
24. 2 in Solution Studied by NMR. Biochemistry 1991, 30, 1372-1385.
25. (c) Conte, M. R.; Jenkins, T. C.; Lane, A. N. Interaction of Minor Groove-Binding Diamidine Ligands with an Asymmetric DNA Duplex: NMR and Molecular Modelling Studies. Eur. J. Biochem. 1995, 229, 433-444.
26. (a) Kopka, M. L.; Yoon, C.; Goodsell, D.; Pjura, P.; Dickerson, R. E. The Molecular Origin of DNA-Drug Specificity in Netropsin and Distamycin. Proc. Natl. Acad. Sci. U.SA. 1985, 82, 1376-1380.
27. (b) Lown, J. W. Lexitropsins: Rational Design of DNA Sequence Reading Agents as Novel Anti-Cancer Agents and Potential Cellular Probes. Anti-Cancer Drug Des. 1988, 3, 25-40.
28. Osland, A.; Kleppe, K. Polyamine Induced Aggregation of DNA. Nucleic Acids Res. 1977, 4, 685-695.
29. See, for example: (a) Bailly, C.; Helbecque, N.; Hénichart, J. P.; Colson, P.; Houssier, C.; Rao, K. E.; Shea, R. G.; Lown, J. W. Molecular Recognition Between Oligopeptides and Nucleic Acids: DNA Sequence Specificity and Binding Properties of an Acridine-Linked Netropsin Hybrid Ligand. J. Mol. Recognit. 1990, 3, 26-35. (b) Bailly, C.; Hénichart, J.-P. Molecular Pharmacology of Intercalator-Groove Binder Hybrid Molecules. In Molecular Aspects of Anticancer Drug-DNA Interactions; Neidle, S., Waring, M., Eds.; Macmillan Press Ltd.: London, U.K., 1994; Vol. 2, pp 162-196.
30. See, for example: (a) Bailly, C.; Helbecque, N.; Hénichart, J. P.; Colson, P.; Houssier, C.; Rao, K. E.; Shea, R. G.; Lown, J. W. Molecular Recognition Between Oligopeptides and Nucleic Acids: DNA Sequence Specificity and Binding Properties of an Acridine-Linked Netropsin Hybrid Ligand. J. Mol. Recognit. 1990, 3, 26-35. (b) Bailly, C.; Hénichart, J.-P. Molecular Pharmacology of Intercalator-Groove Binder Hybrid Molecules. In Molecular Aspects of Anticancer Drug-DNA Interactions; Neidle, S., Waring, M., Eds.; Macmillan Press Ltd.: London, U.K., 1994; Vol. 2, pp 162-196.
31. McConnaughie, A. W. Ph.D. Thesis, University of London, England, 1993.
32. ω and OH Protected 2-[(2-Aminoethyl)aminolethanol. Polish J. Chem. 1995, 69, 632-634.
33. Jenkins, T. C.; Parrick, J.; Porssa, M. DNA-Binding Properties of Nitroarene Oligopeptides Designed as Hypoxia-Selective Agents. Anti-Cancer Drug Des. 1994, 9, 477-493.
34. Kelland, L. R.; Abel, G.; McKeage, M. J.; Jones, M.; Goddard, P. M.; Valenti, M.; Murrer, B. A.; Harrap, K. R. Preclinical Antitumor Evaluation of Bis-acetato-ammine-dichlorocyclohexylamine Platinum(IV): an Orally Active Platinum Compound. Cancer Res. 1993, 53, 2581-2586.
35. Antonini, I.; Polucci, P.; Cola, D.; Bontemps-Gracz, M.; Pescalli, N.; Menta, E.; Martelli, S. Pyrimido[4,5,6-kl]acridines, a New Class of Potential Anticancer Agents. Synthesis and Biological Evaluation. Anti-Cancer Drug Des. 1996, 11, 339-349.
36. Lown, J. W.; Krowicki, K.; Baizarini, J.; Newman, R. A.; De Clercq, E. Novel Linked Antiviral and Antitumor Agents Related to Netropsin and Distamycin: Synthesis and Biological Evaluation. J. Med. Chem. 1989, 32, 2368-2375.