Novel lavendamycin analogues as antitumor agents: Synthesis, in vitro cytotoxicity, structure-metabolism, and computational molecular modeling studies with NAD(P)H:quinone oxidoreductase 1

Journal of Medicinal Chemistry

Volumn 48, Issue 24, 2005, Pages 7733-7749

  Hassani, Mary ^b   Cai, Wen ^a   Holley, David C ^c   Lineswala, Jayana P ^a   Maharjan, Babu R ^a   Ebrahimian, G Reza ^a   Seradj, Hassan ^a   Stocksdale, Mark G ^a   Mohammadi, Farahnaz ^a   Marvin, Christopher C ^a   Gerdes, John M ^c   Beall, Howard D ^b   Behforouz, Mohammad ^a  

^a BALL STATE UNIVERSITY   (United States)

^b UNIVERSITY OF MONTANA   (United States)

^c UNIVERSITY OF MONTANA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7 AMINO 6 CHLORO 2 FORMYLQUINOLINE 5,8 DIONE; ALDEHYDE; ANTINEOPLASTIC AGENT; DECARBOXY 2' (HYDROXYMETHYL)NORLAVENDAMYCIN; INDOLOPYRIDINE; LAVENDAMYCIN DERIVATIVE; PYRIDINE DERIVATIVE; QUININOLINE 5,6 DIONE ALDEHYDE; QUINOLINE DERIVATIVE; QUINOLINEDIONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE DEHYDROGENASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE QUINONE OXIDOREDUCTASE I; TRYPTAMINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; BINDING SITE; CANCER CELL; CANCER CELL CULTURE; CELL STRAIN BE NQ; CELL STRAIN BE WT; COLON ADENOCARCINOMA; CONTROLLED STUDY; CYTOTOXICITY; DRUG BINDING; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HYDROGEN BOND; MOLECULAR MODEL; PICTET SPENGLER REACTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANTINEOPLASTIC AGENTS; BINDING SITES; CELL LINE, TUMOR; DRUG SCREENING ASSAYS, ANTITUMOR; ELECTROCHEMISTRY; HUMANS; HYDROGEN BONDING; MODELS, MOLECULAR; NAD(P)H DEHYDROGENASE (QUINONE); OXIDATION-REDUCTION; STREPTONIGRIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 28144451459     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm050758z     Document Type: Article

References (66)

1. Workman, P. Keynote address: Bioreductive mechanisms. Int. J. Radiat. Oncol. Biol. Phys. 1992, 22, 631-637.
2. Rooseboom, M.; Commandeur, J. N.; Vermeiden, N. P. Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol. Rev. 2004, 56, 53-102.
3. Beall, H. D.; Winski, S. I. Mechanisms of action of quinone-containing alkylating agents. I: NQO1-directed drug development. Front. Biosci. 2000, 5, 639-648.
4. Phillips, R. M. Prospects for bioreductive drug development. Exp. Opin. Invest. Drugs 1998, 7, 905-928.
5. Workman, P. Enzyme-directed bioreductive drug development revisited: A commentary on recent progress and future prospects with emphasis on quinone anticancer agents and quinone metabolizing enzymes, particularly DT-diaphorase. Oncol. Res. 1994, 6, 461-475.
6. Skelly, J. V.; Sanderson, M. R.; Suter, D. A.; Baumann, U.; Read, M. A.; Gregory, D. S.; Bennett, M.; Hobbs, S. M.; Neidle, S. Crystal structure of human DT-diaphorase: A model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954). J. Med. Chem. 1999, 42, 4325-4330.
7. Danson, S.; Ward, T. H.; Butler, J.; Ranson, M. DT-diaphorase: A target for new anticancer drugs. Cancer Treat. Rev. 2004, 30, 437-449.
8. Lind, C.; Cadenas, E.; Hochstein, P.; Ernster, L. DT-diaphorase: Purification, properties, and function. Methods Enzymol. 1990, 186, 287-301.
9. Faig, M.; Bianchet, M. A.; Talalay, P.; Chen, S.; Winski, S.; Ross, D.; Amzel, L. M. Structures of recombinant human and mouse NAD(P)H: quinone oxidoreductases: Species comparison and structural changes with substrate binding and release. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 3177-3182.
10. Li, R.; Bianchet, M. A.; Talalay, P.; Amzel, L. M. The three-dimensional structure of NAD(P)H: quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: Mechanism of the two-electron reduction. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8846-8850.
11. Eliasson, M.; Bostrom, M.; DePierre, J. W. Levels and subcellular distributions of detoxifying enzymes in the ovarian corpus luteum of the pregnant and non-pregnant pig. Biochem. Pharmacol. 1999, 58, 1287-1292.
12. Winski, S. L.; Koutalos, Y.; Bentley, D. L.; Ross, D. Subcellular localization of NAD(P)H:quinone oxidoreductase 1 in human cancer cells. Cancer Res. 2002, 62, 1420-1424.
13. Ernster, L. DT Diaphorase. Methods Enzymol. 1967, 10, 309-317.
14. Ernster, L. DT Diaphorase: A historical review. Chem. Scripta 1987, 27A, 1-13.
15. Siegel, D.; Gibson, N. W.; Preusch, P. C.; Ross, D. Metabolism of mitomycin C by DT-diaphorase: Role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells. Cancer Res. 1990, 50, 7483-7489.
16. Walton, M. I.; Smith, P. J.; Workman, P. The role of NAD(P)H: quinone reductase (EC 1.6.99.2, DT-diaphorase) in the reductive bioactivation of the novel indoloquinone antitumor agent EO9. Cancer Commun. 1991, 3, 199-206.
17. Siegel, D.; Beall, H. D.; Senekowitsch, C.; Kasai, M.; Arai, H.; Gibson, N. W.; Ross, D. Bioreductive activation of mitomycin C by DT-diaphorase. Biochemistry 1992, 31, 7879-7885.
18. Naylor, M. A.; Swann, E.; Everett, S. A.; Jaffar, M.; Nolan, J.; Robertson, N.; Lockyer, S. D.; Patel, K. B.; Dennis, M. F.; Stratford, M. R.; Wardman, P.; Adams, G. E.; Moody, C. J.; Stratford, I. J. Indolequinone antitumor agents: Reductive activation and elimination from (5-methoxy-1-methyl- 4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro. J. Med. Chem. 1998, 41, 2720-2731.
19. Siegel, D.; Gibson, N. W.; Preusch, P. C.; Ross, D. Metabolism of diaziquone by NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase): Role in diaziquone-induced DNA damage and cytotoxicity in human colon carcinoma cells. Cancer Res. 1990, 50, 7293-7300.
20. Schlager, J. J.; Powis, G. Cytosolic NAD(P)H:(quinone-acceptor)- oxidoreductase in human normal and tumor tissue: Effects of cigarette smoking and alcohol. Int. J. Cancer 1990, 45, 403-409.
21. Malkinson, A. M.; Siegel, D.; Forrest, G. L.; Gazdar, A. F.; Oie, H. K.; Chan, D. C.; Bunn, P. A.; Mabry, M.; Dykes, D. J.; Harrison, S. D.; Ross, D. Elevated DT-diaphorase activity and messenger RNA content in human non small cell lung carcinoma: Relationship to the response of lung tumor xenografts to mitomycin C. Cancer Res. 1992, 52, 4752-4757.
22. Cresteil, T.; Jaiswal, A. K. High levels of expression of the NAD-(P)H: quinone oxidoreductase (NQO1) gene in tumor cells compared to normal cells of the same origin. Biochem. Pharmacol. 1991, 42, 1021-1027.
23. Rampling, R.; Cruickshank, G.; Lewis, A. D.; Fitzsimmons, S. A.; Workman, P. Direct measurement of pO2 distribution and bioreductive enzymes in human malignant brain tumors. Int. J. Radiat. Oncol. Biol. Phys. 1994, 29, 427-431.
24. Mikami, K.; Naito, M.; Ishiguro, T.; Yano, H.; Tomida, A.; Yamada, T.; Tanaka, N.; Shirakusa, T.; Tsuruo, T. Immunological quantitation of DT-diaphorase in carcinoma cell lines and clinical colon cancers: Advanced tumors express greater levels of DT-diaphorase. Jpn. J. Cancer Res. 1998, 89, 910-915.
25. Faig, M.; Bianchet, M. A.; Winski, S.; Hargreaves, R.; Moody, C. J.; Hudnott, A. R.; Ross, D.; Amzel, L. M. Structure-based development of anticancer drugs: Complexes of NAD(P)H: quinone oxidoreductase 1 with chemotherapeutic quinones. Structure 2001, 9, 659-667.
26. Winski, S. L.; Faig, M.; Bianchet, M. A.; Siegel, D.; Swann, E.; Fung, K.; Duncan, M. W.; Moody, C. J.; Amzel, L. M.; Ross, D. Characterization of a mechanism-based inhibitor of NAD(P)H: quinone oxidoreductase 1 by biochemical, X-ray crystallographic, and mass spectrometric approaches. Biochemistry 2001, 40, 15135-15142.
27. Zhou, Z.; Fisher, D.; Spidel, J.; Greenfield, J.; Patson, B.; Fazal, A.; Wigal, C.; Moe, O. A.; Madura, J. D. Kinetic and docking studies of the interaction of quinones with the quinone reductase active site. Biochemistry 2003, 42, 1985-1994.
28. Cavelier, G.; Amzel, L. M. Mechanism of NAD(P)H: quinone reductase: Ab initio studies of reduced flavin. Proteins: Struct. Funct. Genet. 2001, 43, 420-432.
29. Doyle, T. W.; Balitz, D. M.; Grulich, R. E.; Nettleton, D. E.; Gould, S. J.; Tann, C.; Moews, A. E. Structure determination of lavendamycin, a new antitumor antibiotic from Streptomyces lavendulae. Tetrahedron Lett. 1981, 22, 4595-4598.
30. Balitz, D. M.; Bush, J. A.; Bradner, W. T.; Doyle, T. W.; O'Herron, F. A.; Nettleton, D. E. Isolation of lavendamycin, a new antibiotic from Streptomyces lavendulae. J. Antibiot. (Tokyo) 1982, 35, 259-265.
31. 2: Evidence for an oxidative β-carboline cleavage. J. Am. Chem. Soc. 1985, 107, 5831-5832.
32. Erickson, W. R.; Gould, S. J. Streptonigrin Biosynthesis. 8. Evidence for the involvement of a new Shikimate pathway product and a new route to quinolines. J. Am. Chem. Soc. 1987, 109, 620-621.
33. Rao, K. V.; Biemann, K.; Woodward, R. B. The structure of Streptonigrin. J. Am. Chem. Soc. 1963, 85, 2532-2533.
34. Boger, D. L.; Yasuda, M.; Mitscher, L. A.; Drake, S. D.; Kites, P. A.; Thompson, S. C. Streptonigrin and lavendamycin partial structures. Probes for the minimum, potent pharmacophore of streptonigrin, lavendamycin, and synthetic quinoline-5,8-diones. J. Med. Chem. 1987, 30, 1918-1928.
35. Hackethal, C. A.; Golbey, R. B.; Tan, C. T.; Karnofsky, D. A.; Burchenal, J. H. Clinical observations on the effects of Streptonigrin in patients with neoplastic disease. Antibiot. Chemother. 1961, 11, 178-183.
36. Fang, Y.; Linardic, C. M.; Richardson, D. A.; Cai, W.; Behforouz, M.; Abraham, R. T. Characterization of the cytotoxic activities of novel analogues of the antitumor agent, lavendamycin. Mol. Cancer Ther. 2003, 2, 517-526.
37. Behforouz, M.; Merriman, R. L. Lavendamycin analogues and methods of making and using them. U.S. Patent 5525611, 1996.
38. Behforouz, M.; Cai, W.; Stocksdale, M. G.; Lucas, J. S.; Jung, J. Y.; Briere, D.; Wang, A.; Katen, K. S.; Behforouz, N. C. Novel lavendamycin analogues as potent HIV-reverse transcriptase inhibitors: Synthesis and evaluation of anti-reverse transcriptase activity of amide and ester analogues of lavendamycin. J. Med. Chem. 2003, 46, 5773-5780.
39. Kende, A. S.; Ebetino, F. H. The regiospecific total synthesis of lavendamycin methyl ester. Tetrahedron Lett. 1984, 25, 923-926.
40. Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. Total synthesis of lavendamycim methyl ester. J. Org. Chem. 1985, 50, 5790-5795.
41. Behforouz, M.; Gu, Z.; Cai, W.; Horn, M. A.; Ahmadian, M. A highly concise synthesis of lavendamycin methyl ester. J. Org. Chem. 1993, 58, 7089-7091.
42. Behforouz, M.; Haddad, J.; Cai, W.; Arnold, M. B.; Mohammadi, F.; Sousa, A. C.; Horn, M. A. Highly efficient and practical syntheses of lavendamycin methyl ester and related novel quinolindiones. J. Org. Chem. 1996, 61, 6552-6555.
43. Behforouz, M.; Zarrinmayeh, H.; Ogle, M. E.; Riehle, T. J.; Bell, F. W. β-Carbolines derived from β-methyltryptophan and a stereoselective synthesis of (2RS, 3SR)-β-methyltryptophan methyl ester. J. Heterocycl. Chem. 1988, 25, 1627-1632.
44. Behforouz, M.; Haddad, J.; Cai, W.; Gu, Z. Chemistry of quinoline-5,8-diones. J. Org. Chem. 1998, 63, 343-346.
45. Seradj, H.; Cai, W.; Erasga, N. O.; Chenault, D. V.; Knuckles, K. A.; Ragains, J. R.; Behforouz, M. Total synthesis of novel 6-substituted lavendamycin antitumor agents. Org. Lett. 2004, 6, 473-476.
46. Barret, R.; Daudon, M. Oxidation of phenols to quinones by bis-(trifluoroacetoxy)iodobenzene. Tetrahedron Lett. 1990, 31, 4871-4872.
47. Tolstikov, V. V.; Holpne Kozlova, N. V.; Oreshkina, T. D.; Osipova, T. V.; Preobrazhenskaya, M. N.; Sztaricskai, F.; Balzarini, J.; De Clercq, E. Amides of antibiotic Streptonigrin and amino dicarboxylic acids or aminosugars. Synthesis and biological evaluation. J. Antibiot. (Tokyo) 1992, 45, 1020-1025.
48. Cotterill, A. S.; Moody, C. J.; Mortimer, R. J.; Norton, C. L.; O'Sullivan, N.; Stephens, M. A.; Stradiotto, N. R.; Swann, E.; Stratford, I. J. Cyclopropamitosenes, novel bioreductive anticancer agents. Synthesis, electrochemistry, and biological activity of 7-substituted Cyclopropamitosenes and related indolequinones. J. Med. Chem. 1994, 37, 3834-3843.
49. Beall, H. D.; Winski, S.; Swann, E.; Hudnott, A. R.; Cotterill, A. S.; O'Sullivan, N.; Green, S. J.; Bien, R.; Siegel, D.; Ross, D.; Moody, C. J. Indolequinone antitumor agents: Correlation between quinone structure, rate of metabolism by recombinant human NAD(P)H: quinone oxidoreductase, and in vitro cytotoxicity. J. Med. Chem. 1998, 41, 4755-4766.
50. Swann, E.; Barraja, P.; Oberlander, A. M.; Gardipee, W. T.; Hudnott, A. R.; Beall, H. D.; Moody, C. J. Indolequinone antitumor agents: Correlation between quinone structure and rate of metabolism by recombinant human NAD(P)H: quinone oxidoreductase. Part 2. J. Med. Chem. 2001, 44, 3311-3319.
51. Fryatt, T.; Pettersson, H. I.; Gardipee, W. T.; Bray, K. C.; Green, S. J.; Slawin, A. M.; Beall, H. D.; Moody, C. J. Novel quinoline-quinone antitumor agents: Structure-metabolism studies with NAD(P)H: quinone oxidoreductase (NQO1). Bioorg. Med. Chem. 2004, 12, 1667-1687.
52. Phillips, R. M.; Naylor, M. A.; Jaffar, M.; Doughty, S. W.; Everett, S. A.; Breen, A. G.; Choudry, G. A.; Stratford, I. J. Bioreductive activation of a series of indolequinones by human DT-diaphorase: Structure-activity relationships. J. Med. Chem. 1999, 42, 4071-4080.
53. Winski, S. L.; Hargreaves, R. H.; Butler, J.; Ross, D. A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: Identification of a new aziridinyl-hfbenzoquinone, RH1, as a NQO1-directed antitumor agent. Clin. Cancer Res. 1998, 4, 3083-3088.
54. Phillips, R. M.; Jaffar, M.; Maitland, D. J.; Loadman, P. M.; Shnyder, S. D.; Steans, G.; Cooper, P. A.; Race, A.; Patterson, A. V.; Stratford, I. J. Pharmacological and biological evaluation of a series of substituted 1,4-naphthoquinone bioreductive drugs. Biochem. Pharmacol. 2004, 68, 2107-2116.
55. Suleman, A.; Skibo, E. B. A comprehensive study of the active site residues of DT-diaphorase: Rational design of benzimidazolediones as DT-diaphorase substrates. J. Med. Chem. 2002, 45, 1211-1220.
56. Hendriks, H. R.; Pizao, P. E.; Berger, D. P.; Kooistra, K. L.; Bibby, M. C.; Boven, E.; Dreef-van der Meulen, H. C.; Henrar, R. E. C.; Fiebig, H. H.; Double, J. A.; Hornstra, H. W.; Pinedo, H. M.; Workman, P.; Schwartsmann, G. E09: A novel bioreductive alkylating indoloquinone with preferential solid tumour activity and lack of bone marrow toxicity in preclinical models. Eur. J. Cancer 1993, 29A, 897-906.
57. Abe, N.; Nakakita, Y.; Nakamura, T.; Enoki, N.; Uchida, H.; Takeo, S.; Munekata, M. Novel cytocidal compounds, oxopropalines from Streptomyces sp. G324 producing lavendamycin. I. Taxonomy of the producing organism, fermentation, isolation and biological activities. J. Antibiot. (Tokyo) 1993, 46, 1672-1677.
58. SYBYL molecular modeling software; SYBYL 6.9.1 ed.; Tripos Inc.: St. Louis, MO.
59. Lemmen, C.; Lengauer, T. Time-efficient flexible superposition of medium-sized molecules. J. Comput.-Aided Mol. Des. 1997, 11, 357-368.
60. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A fast flexible docking method using an incremental construction algorithm. J. Mol. Biol. 1996, 261, 470-489.
61. Eldridge, M. D.; Murray, C. W.; Auton, T. R.; Paolini, G. V.; Mee, R. P. Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J. Comput.-Aided Mol. Des. 1997, 11, 425-445.
62. Kuntz, I. D.; Blaney, J. M.; Oatley, S. J.; Langridge, R.; Ferrin, T. E. A geometric approach to macromolecule-ligand interactions. J. Mol. Biol. 1982, 161, 269-288.
63. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
64. Muegge, I.; Martin, Y. C. A general and fast scoring function for protein-ligand interactions: A simplified potential approach. J. Med. Chem. 1999, 42, 791-804.
65. Allen, C. F. H.; Spangler, F. W.; Webster, E. R. Ethylenimine. Org. Synth. 1963, Coll. Vol. IV, 433-435.
66. DeLano, W. L. The PyMOL molecular graphics system; Py MOLX11Hybrid ed.; DeLano Scientific: San Carlos, CA.