Rational design, synthesis, and biological evaluation of bis(pyrimido[5,6,1-de]acridines) and bis(pyrazolo[3,4,5-kl]acridine-5- carboxamides) as new anticancer agents

Journal of Medicinal Chemistry

Volumn 47, Issue 21, 2004, Pages 5244-5250

  Antonini, Ippolito ^a   Polucci, Paolo ^a,b   Magnano, Amelia ^a   Sparapani, Silvia ^a   Martelli, Sante ^a  

^a UNIVERSITY OF CAMERINO   (Italy)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,9 BIS[2 [2 (DIMETHYLAMINO)ETHYL] 1,3,7 TRIOXO 2,3 DIHYDRO 1H,7H PYRIMIDO[5,6,1 DE]ACRIDIN 6 YL] 5 METHYL 1,5,9 TRIAZANONANE; 1,9 BIS[2 [2 (DIMETHYLAMINO)ETHYL] 2,6 DIHYDROPYRAZOLO[3,4,5 KL]ACRIDINE 5 CARBONYL] 5 METHYL 1,5,9 TRIAZANONANE; 1,9 BIS[2 [2 (DIMETHYLAMINO)ETHYL] 9 HYDROXY 1,3,7 TRIOXO 2,3 DIHYDRO 1H,7H PYRIMIDO[5,6,1 DE]ACRIDIN 6 YL] 5 METHYL 1,5,9 TRIAZANONANE; 1,9 BIS[2 [2 (DIMETHYLAMINO)ETHYL] 9 NITRO 1,3,7 TRIOXO 2,3 DIHYDRO 1H,7H PYRIMIDO[5,6,1 DE]ACRIDIN 6 YL] 5 METHYL 1,5,9 TRIAZANONANE; ANTINEOPLASTIC AGENT; BIS(ACRIDINE 4 CARBOXAMIDE) DERIVATIVE; BIS(PYRAZOLO[3,4,5 KL]ACRIDINE 5 CARBOXAMIDE) DERIVATIVE; BIS(PYRIMIDO[5,6,1 DE]ACRIDINE) DERIVATIVE; MONOMER; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASSAY; CANCER CELL CULTURE; COLON ADENOCARCINOMA; COMPARATIVE STUDY; CONTROLLED STUDY; CYCLIZATION; CYTOTOXICITY; DRUG ACTIVITY; DRUG BINDING; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG DNA BINDING; DRUG EFFICACY; DRUG POTENCY; DRUG PREFERENCE; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; FLUOROMETRY; HOLLOW FIBER; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

EID: 4744365801     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049706k     Document Type: Article

References (28)

1. McRipley, R. J.; Burns-Horwitz, P. E.; Czerniak, P. M.; Diamond, R. J.; Diamond, M. A.; Miller, J. L. D.; Page, R. J.; Dexter, D. L.; Chen, S. F.; Sun, J. H. Efficacy of DMP 840: a Novel Bis-Naphthalimide Cytotoxic Agent with Human Solid Tumor Xenograft Selectivity. Cancer Res. 1994, 54, 159-164.
2. Brana, M. F.; Castellano, J. M.; Moran, M.; Perez de Vega, M. J.; Perron, D.; Conlon, D.; Bousquet, P. F.; Romerdahl, C. A.; Robinson, S. P. Bis-Naphthalimides 3: Synthesis and Antitumor Activity of N,N′-Bis[2-(1,8- naphthalimido)ethyl]alkane-diamines. Anti-Cancer Drug Des. 1996, 11, 297-309.
3. Nitiss, J. L.; Zhou, J.; Rose, A., Hsiung, Y.; Gale, K. C.; Osheroff, N. The Bis(naphthalimide) DMP-840 Causes Cytotoxicity by Its Action against Eukaryotic Topoisomerase II. Biochemistry 1998, 37, 3078-3085.
4. O'Reilly, S.; Baker, S. D., Sartorius, S.; Rowinsky, E. K.; Finizio, M.; Lubiniecki, G. M.; Grochow, L. B.; Gray, J. E.; Pieniaszek, H. J.; Donehower, R. C. A Phase I and Pharmacologic Study of DMP 840 Administered by 24-Hour Infusion. Ann. Oncol. 1998, 9, 101-104.
5. Braña, M. F.; Castellano, J. M.; Perron, D.; Maher, C.; Conlon, D.; Bousquet, P. F.; George, J.; Qian, X.-D.; Robinson, S. P. Chromophore-Modified Bis-Naphthalimides: Synthesis and Antitumor Activity of Bis-Dibenz[de,h] isoquinoline-1,3-diones. J. Med. Chem. 1997, 40, 449-454.
6. Bousquet, P. F.; Brana, M. F.; Conlon, D.; Fitzgerald, K. M.; Perron, D.; Cocchiaro, C.; Miller, R.; Moran, M.; George, J.; Qian, X. D. Preclinical Evaluation of LU 79553: a Novel Bis-Naphthalimide with Potent Antitumor Activity. Cancer Res. 1995, 55, 1176-1180.
7. Cholpdy, W. M.; Hernandez, L.; Hassner, L.; Scudiero, D. A.; Djurickovic, D. B.; Michejda, C. J. Bisimidazoacridones and Related Compounds: New Antineoplastic Agents with High Selectivity against Colon Tumors. J. Med. Chem. 1995, 38, 3043-3052.
8. Gamage, S. A.; Spicer, J. A.; Atwell, G. J.; Finlay, G. J.; Baguley, B. C.; Denny, W. A. Structure-Activity Relationships for Substituted Bis(acridine-4-carboxamides): A New Class of Anticancer Agents. J. Med. Chem. 1999, 42, 2383-2393.
9. Gamage, S. A.; Spicer, J. A.; Finlay, G. J.; Stewart, A. J.; Charlton, P.; Baguley, B. C.; Denny, W. A. Dicationic Bis(9-methylphenazine-1- carboxamides): Relationships between Biological Activity and Linker Chain Structure for a Series of Potent Topoisomerase Targeted Anticancer Drugs. J. Med. Chem. 2001, 44, 1407-1415.
10. Chaires, J. B.; Leng, F.; Przewloka, T.; Fokt, I.; Ling, Y.-H.; Perez-Soler, R.; Priebe, W. Structure-Based Design of a New Bisintercalating Anthracycline Antibiotic. J. Med. Chem. 1997, 40, 261-266.
11. Antonini, I.; Polucci, P.; Magnano, A.; Gatto, B.; Palumbo, M.; Menta, E.; Pescalli, N.; Martelli S. Design, Synthesis, and Biological Properties of New Bis(acridine-4-carboxamides) as Anticancer Agents. J. Med. Chem. 2003, 46, 3109-3115.
12. Antonini, I.; Polucci, P.; Jenkins, T. C.; Kelland, L. R.; Menta, E.; Pescalli, N.; Stefanska, B.; Mazerski, J.; Martelli, S. 1-[(ω-Aminoalkyl) amino]-4-[N-(ω-aminoalkyl)carbamoyl]-9-oxo-9,10-dihydroacridines as Intercalating Cytotoxic Agents: Synthesis, DNA Binding, and Biological Evaluation. J. Med. Chem. 1997, 40, 3749-3755.
13. (a) Antonini, I.; Cola, D.; Polucci, P.; Bontemps-Gracz, M.; Borowski, E.; Martelli, S. Synthesis of (dialkylamino)alkyl-disubstituted pyrimido[5,6,1-de]acridines, a novel group of anticancer agents active on a multidrug resistant cell line. J. Med. Chem. 1995, 38, 3282-3286.
14. (b) Antonini, I.; Polucci, P.; Kelland, L. R.; Menta, E.; Pescalli, N.; Martelli S. 2,3-Dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione Derivatives: A Class of Cytotoxic Agents Active on Multidrug Resistant Cell Lines. Synthesis, Biological Evaluation and Structure-Activity Relationships. J. Med. Chem. 1999, 42, 2535-2541.
15. (c) Antonini, I. DNA-binding Antitumor Agents: from Pyrimido[5,6,1-de] acridines to Other Intriguing Classes of Acridine Derivatives. Curr. Med. Chem. 2002, 9, 1701-1716.
16. (a) Antonini, I.; Polucci, P.; Magnano, A.; Martelli S. Synthesis, Antitumor Cytotoxicity, and DNA-Binding of Novel N-5,2-Di-(ω-aminoalkyl)- 2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamides. J. Med. Chem. 2001, 44, 3329-3333.
17. (b) Bontemps-Gracz, M. M.; Kupiec, A.; Antonini, I.; Borowski, E. The ability to overcome multidrug resistance of tumor cell lines by novel acridine cytostatics with condensed heterocyclic rings. Acta Biochim. Pol. 2002, 49, 87-92.
18. (a) 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. (b) Jenkins, T. C. Optical Absorbance and Fluorescence Techniques for Measuring DNA-Drug Interactions. In Methods in Molecular Biology, Vol. 90: Drug-DNA Interaction Protocols; Fox, K. R., Ed.; Humana Press: Totawa, NJ, 1997; Chapter 14, pp 195-218.
20. (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.
21. (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.
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. We thank the Developmental Therapeutics Program of the NCI, Bethesda, MD, for performing the in vitro and in vivo anticancer evaluations.
24. 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. C.; 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.
25. (a) Mosman, T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assay. J. Immunol. Methods 1983, 65, 55-63.
26. (b) Alley, M. C.; Scudiero, D. A.; Monks, A.; Hursey, M. L.; Czerwinsky, M. J.; Fine, D. L.; Abbott, B. J.; Mayo, J. G.; Shoemaker, R. H.; Boyd, M. R. Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay. Cancer Res. 1988, 48, 589-601.
27. 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.
28. Boyd, M. R.; Paull, K. D. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 1995, 34, 91-109.