Antitumor agents. 1. Synthesis, biological evaluation, and molecular modeling of 5H-pyrido[3,2-a]phenoxazin-5-one, a compound with potent antiproliferative activity

Journal of Medicinal Chemistry

Volumn 45, Issue 24, 2002, Pages 5205-5216

  Bolognese, Adele ^a   Correale, Gaetano ^a   Manfra, Michele ^a   Lavecchia, Antonio ^a   Mazzoni, Orazio ^a   Novellino, Ettore ^a   Barone, Vincenzo ^a   Pani, Alessandra ^b   Tramontano, Enzo ^b   La Colla, Paolo ^b   Murgioni, Chiara ^b   Serra, Ilaria ^b   Setzu, Giovanna ^b   Loddo, Roberta ^b  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 ACETYLAMINO 3H PHENOXAZIN 3 ONE; 2 AMINO 1,9 DIACETYL 3H PHENOXAZIN 3 ONE; 2 AMINO 3H PHENOXAZIN 5 ONE; 3H PHENOXAZIN 3 ONE; 5H PYRIDO[3,2 A]PHENOTHIAZIN 5 ONE; 5H PYRIDO[3,2 A]PHENOXAZIN 5 ONE; ANTINEOPLASTIC AGENT; DACTINOMYCIN; NITROGEN; PHENOXAZINE DERIVATIVE; POLYCYCLIC HYDROCARBON; PYRIDINE DERIVATIVE; QUINONE DERIVATIVE; UNCLASSIFIED DRUG;

ANALYTIC METHOD; ARTICLE; BIOLOGY; CELL CLONE; CHROMATOPHORE; DNA BINDING; ELECTRICITY; EVALUATION; HUMAN; LIQUID; MOLECULAR MECHANICS; MOLECULAR MODEL; PROTEIN EXPRESSION; PROTON NUCLEAR MAGNETIC RESONANCE; SOLID TUMOR; SPECTROSCOPY; SYNTHESIS; TUMOR CELL; ULTRAVIOLET RADIATION;

ANTINEOPLASTIC AGENTS; CELL DIVISION; DNA; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INTERCALATING AGENTS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; OXAZINES; SPECTROPHOTOMETRY, ULTRAVIOLET; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TUMOR CELLS, CULTURED;

EID: 0037153234     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020913z     Document Type: Article

References (39)

1. Butenandt, A.; Shäfer, W. Ommochromes. In Recent Progress in the Chemistry of Natural and Synthetic Matters and Related Fields; Gore, T. S., Yoshi, B. S., Suthankar, S. V., Tilak, B. D., Eds.; Academic Press: New York, 1962; pp 14-33.
2. Bolognese, A.; Piscitelli, C.; Scherillo, G. Formation of dihydrotriphenodioxazines and dihydroisotriphenodioxazines by acidic treatment of some substituted 3H-phenoxazin-3-ones: Isolation and characterization. A new perspective in the chemistry of ommochromes. J. Org. Chem. 1983, 48, 3649-3652.
3. Ionescu, M.; Mantsch, H. Phenoxazine. Adv. Heterocycl. Chem. 1967, 8, 83-110.
4. Wakelin, L. P. G.; Waring, M. J. DNA intercalating agents. In Comprehensive Medicinal Chemistry; Sammes, P. G., Ed.; Pergamon Press: Oxford, U.K., 1990; Vol. 2, pp 703-724.
5. Kamitori, S.; Takusagawa, F. Crystal structure of the 2:1 Complex between d(GAAGCTTC) and the anticancer drug actinomycin D. J. Mol. Biol. 1992, 225, 445-56.
6. Kamitori, S.; Takusagawa, F. Multiple binding modes of anticancer drug actinomycin-D-X-ray, molecular modeling, and spectroscopic studies of D(GAAGCTTC)(2)-actinomycin-D complexes and its host DNA. J. Am. Chem. Soc. 1994, 116, 4154-4165.
7. Shinomiya, M.; Chu, W.; Carlson, R. G.; Weaver, R. F.; Takusagawa, F. Structural, physical, and biological characteristics of RNA. DNA binding agent N8-actinomycin D. Biochemistry 1995, 34, 8481-8491.
8. Takusagawa, F.; Takusagawa, K. T.; Carlson, R. G.; Weaver, R. F. Selectivity of F8-actinomycin D for RNA:DNA hybrids and its anti-leukemia activity. Bioorg. Med. Chem. 1997, 5, 1197-1207.
9. Meienhofer, I.; Atherton, E. Structure - Activity Relationships Among the Semisynthetic Antibiotics; Perlman, D., Ed.; Academic Press: New York, 1977; pp 427-529.
10. Bolognese, A.; Scherillo, G.; Schäfer, W. Reaction of 2-aminophenol and p-benzoquinone in acetic acid. J. Heterocycl. Chem. 1986, 23, 1003-1006.
11. Nan'ya, S.; Maekawa, E.; Hayakawa, H.; Kitaguchi, Y.; Ueno, Y. Synthesis of 5H-pyrido[2,3-a]phenoxazin-5-one and 5h-pyrido [3,2-a] phenoxazin-5-one derivatives. J. Heterocycl. Chem. 1985, 22, 1483-1885.
12. Ueno, Y. Synthesis of 5H-pyridophenothiazin-5-ones. Pharmazie 1986, 41, 144.
13. Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A smooth particle Mesh Ewald method. J. Chem. Phys. 1995, 103, 8577-8593.
14. Pratt, Y. T. Quinolinquinones. VI. Reactions with aromatic amines. J. Am. Chem. Soc. 1962, 27, 3905-3910.
15. Fleming, I. Frontier Orbitals and Organic Chemical Reactions; John Wiley & Sons: Chichester, U.K., 1976.
16. Endicott, J. A.; Ling, V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem. 1989, 58, 137-171.
17. Twentyman, P. R. Multidrug resistance strategy for circumventation. Drug News Perspect. 1993, 6, 647-654.
18. Pastan, I.; Gottesman, M. M.; Ueda, K.; Lovelace, E.; Rutherford, A. V.; Willngham, M. C. A Retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 4486-4490.
19. Chen, H. X.; Bamberger, U.; Heckel, A.; Guo, X.; Cheng, Y. C. BIBW 22, a dipyridamole analogue, acts as bifunctional modulator on tumor cells by influencing both P-glycoprotein and nucleoside transport. Cancer Res. 1993, 53, 1974-1977.
20. Gaj, C. L.; Anyanwutaku, I.; Chang, Y. H.; Cheng, Y. C. Decreased drug accumulation without increased drug efflux in a novel MRP-overexpressing multidrug-resistant cell line. Biochem. Pharmacol. 1998, 55, 1199-2110.
21. a of ligands bound to DNA. Biopolymers 1981, 20, 141-154.
22. Misra, V. K.; Honig, B. On the magnitude of the electrostatic contribution to ligand-DNA interactions. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 4691-4695.
23. SYBYL Molecular Modelling System, Version 6.8; Tripos Inc.: St. Louis, MO.
24. Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. CHARMM: A program for macromolecular energy, minimization and dynamics calculations. J. Comput. Chem. 1983, 4, 187-217.
25. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.10; Gaussian, Inc.: Pittsburgh, PA, 1998.
26. Adamo, C.; Barone, V. Toward realiable density functional without adjustable parameters: The PBE0 model. J. Chem. Phys. 1999, 110, 6158-6170.
27. Foresman, J. B.; Frisch, Æ. Exploring Chemistry with Electronic Structure Methods, 2nd Ed.; Gaussian Inc.: Pittsburgh, PA, 1998.
28. Adamo, C.; Cassi, M.; Barone, V. An accurate density functional method for the study of magnetic properties. The PBE0 model. THEOCHEM 1999, 493, 145-157.
29. Adamo, C.; Cassi, M.; Rege, N.; Barone, V. In New Computational Strategies for the Quantum Mechanical Study of Biological System in Condensed Phases, in Theoretical Biochemistry Processes and Properties of Biological Systems, Theretical and Computational Chemistry; Eriksson, L. A., Ed.; Elsevier Science B. D.: New York, 2001; Vol. 9, pp 467-538.
30. Vinter, J. G.; Davis, A.; Saunders, M. R. Strategic approaches to drug design. 1. An integrated software framework for molecular modelling. J. Comput.-Aided Mol. Des. 1987, 1, 31-55.
31. Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. AM1: A new general purpose mechanical molecular model. J. Am. Chem. Soc. 1985, 107, 3902-3909.
32. MOPAC (Version 6.0) is Available from Quantum Chemistry Program Exchange, No. 455.
33. (a) Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, T. E., III; Debolt, S.; Ferguson, D. M.; Seibel, G. L.; Kollman, P. A. AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comput. Phys. Commun. 1995, 91, 1-41.
34. (b) Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, T. E., III; Ferguson, D. M.; Seibel, G.; Singh, U. C.; Weiner, P. K.; Kollman, P. A. AMBER, Version 5.0; Department of Pharmaceutical Chemistry, University of California, San Francisco: San Francisco, CA, 1995.
35. Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J. Am. Chem. Soc. 1995, 117, 5179-5197.
36. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; Meyer, E. F., Jr.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, T. The protein data bank: A computer based archival file for macromolecular structures. J. Mol. Biol. 1977, 112, 535-542.
37. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R.; W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926-935.
38. Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; DiNola, A.; Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984, 81, 3684-3690.
39. Ryckaert, J. P.; Ciccoti, G.; Berendsen, H. J. C. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 1977, 23, 327-341.