Inhibitors of topoisomerase II based on the benzodiimidazole and dipyrroloimidazobenzimidazole ring systems: Controlling DT-diaphorase reductive inactivation with steric bulk

Journal of Medicinal Chemistry

Volumn 43, Issue 4, 2000, Pages 629-638

  Schulz, William G ^a   Skibo, Edward B ^a  

^a ARIZONA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 BENZOQUINONE; 2,6 DI(CHLOROMETHYL) 1,7 DIMETHYLBENZO[1,2 D:4,5 D']DIIMIDAZOLE 4,8 DIONE; 3,7 DIACETOXY 3H,7H 1,2,8,9 TETRAHYDROPYRROLO[1,2 A]PYRROLO[1',2':1,2]IMIDAZO[4,5 F]BENZIMIDAZOLE 5,10 DIONE; 3H,7H 1,2,8,9 TETRAHYDROPYRROLO[1,2 A]PYRROLO[1',2':1,2]IMIDAZO[4,5 F]BENZIMIDAZOLE 5,10 DIONE; DNA; DNA TOPOISOMERASE (ATP HYDROLYSING); DNA TOPOISOMERASE INHIBITOR; HYDROQUINONE; IMIDAZOLE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); TAMOXIFEN; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DRUG SYNTHESIS; ENZYME INACTIVATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; NONHUMAN; RAT;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; DNA; DNA TOPOISOMERASES, TYPE II; ENZYME INHIBITORS; HUMANS; IMIDAZOLES; INHIBITORY CONCENTRATION 50; NAD(P)H DEHYDROGENASE (QUINONE); RATS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; TUMOR CELLS, CULTURED;

EID: 0033997437     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990210q     Document Type: Article

References (35)

1. Ernster, L. DT-diaphorase: Its structure, function, regulation, and role in antioxidant defense and cancer chemotherapy. In Pathophysiology of Lipid Peroxides and Related Free Radicals; Yagi, K.; Ed.; Karger: Basel, 1998; pp 149-168.
2. Rauth, A. M.; Goldberg, Z.; Misra, V. DT-diaphorase: Possible roles in cancer chemotherapy and carcinogenesis. Oncol. Res. 1997, 9, 339-349.
3. Moore, H. W. Bioactivation as a Model for Drug Design Bioreductive Alkylation. Science (Washington, D.C.) 1977, 197, 527-532.
4. Moore, H. W.; Czerniak, R. Naturally Occurring Quinones as Potential Bioreductive Alkylating Agents. Med. Res. Rev. 1981, 1, 249-280.
5. Skibo, E. B. The Discovery of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents - The Design of Selective Antitumor Agents. Curr. Med. Chem. 1996, 2, 900-931.
6. Schulz, W. G.; Islam, E.; Skibo, E. B. Pyrrolo[1,2-a]benzimidazole-Based Quinones and Iminoquinones. The Role of the 3-Substituent on Cytotoxicity. J. Med. Chem. 1995, 38, 109-118.
7. Skibo, E. S.; Gordon, S.; Bess, L.; Boruah, R.; Heileman, J. Studies of Pyrrolo[1,2-a]benzimidazole Quinone DT-Diaphorase Substrate Activity, Topoisomerase II Inhibition Activity, and DNA Reductive Alkylation. J. Med. Chem. 1997, 40, 1327-1339.
8. Skibo, E. B. Pyrrolobenzimidazoles in cancer treatment. Expert Opin. Ther. Patents 1998, 8, 673-701.
9. Islam, I.; Skibo, E. B. Synthesis and Physical Studies of Azamitosene and Iminoazamitosene Reductive Alkylating Agents. Iminoquinone Hydrolytic Stability, Syn/Anti Isomerization, and Electrochemistry. J. Org. Chem. 1990, 55, 3195-3205.
10. Skibo, E. B.; Islam, I.; Schulz, W. G.; Zhou, R.; Bess, L.; Boruah, R. The Organic Chemistry of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents. An Example of Rational Drug Design. Synlett 1996, 297-309.
11. Zimmer, H.; Lankin, D. C.; Horgan, S. W. Oxidations with Potassium Nitrosodisulfonate (Fremy's Radical). The Teuber Reaction. Chem. Rev. 1971, 71, 229-246.
12. Phillips, M. A. The Formation of 2-Substituted Benzimidazoles. J. Chem. Soc. 1928, 2393-2399.
13. Meth-Cohn, O.; Suschitzky, H. Heterocycles by Ring Closure of Ortho-Substituted t-Anilines (The t-Amino Effect). Adv. Heterocycl. Chem. 1972, 14, 211-278.
14. Grantham, R. K.; Meth-Cohn, O. The Formation of Benzimidazolones and Quinoxalines from o-Nitrophenyldialkylanilines: A Reinvestigation. J. Chem. Soc. C 1969, 70-74.
15. Ringdahl, B.; Craig, J. C. Circular Dichroism of 3-Hydroxy-2-pyrrolidone. Acta Chem. Scand. B 1980, 34, 731-733.
16. Paull, D. K.; Shoemaker, R. H.; Hodes, L.; Monks, A.; Scudiero, D. A.; Rubinstein, L.; Plowman, J.; Boyd, M. R. Display and Analysis of Differential Activity of Drugs Against Human Tumor Cell Lines: Development of Mean Graph and COMPARE Algorithm. J. Natl. Cancer Inst. 1989, 81, 1088-1092.
17. Boyd, M. R. Status of the NCI Preclinical Antitumor Drug Discovery Screen. Principles Practices Oncol. (PPO Updates) 1989, 3.
18. Weinstein, J. N.; Myers, T. G.; O'Connor, P. M.; Friend, S. H.; Fornace, A. J.; Kohn, K. W.; Fojo, T.; Bates, S. E.; Rubinstein, L. V.; Anderson, N. L.; Buolamwini, J. K.; W. W. van Osdol, W. W.; Monks, A. P.; Scudiero, D. A.; Sausville, E. A.; Zaharevitz, D. W.; Bunow, B.; Viswanadhan, V. N.; Johnson, G. S.; Wittes, R. E.; Paull, K. D. An Information-Intensive Approach to the Molecular Pharmacology of Cancer. Science 1997, 275, 343-349.
19. Zhou, R.; Skibo, E. B. Chemistry of the Pyrrolo[1,2-a]benzimidazole Antitumor Agents: Influence of the 7-Substituent on the Ability to Alkylate DNA and Inhibit Topoisomerase II. J. Med. Chem. 1996, 39, 4321-4331.
20. Estey, D.; Silberman, L. A.-H. m-AMSA-Induced DNA Strand Breaks: A Potential Measure of the Malignant Phenotype. Proc. Am. Assoc. Cancer Res. 1985, 26, 227.
21. Pommier, Y.; Schwartz, R. E.; Kohn, K. W.; Zwelling, L. A. Formation and Rejoining of Deoxyribonucleic Acid Double-Stranded Breaks induced in Isolated Nuclei by Antineoplastic Intercalating Agents. Biochemistry 1984, 23, 3194-3201.
22. Ross, W.; Rowe, T.; Glisson, F.; Yalowich, J.; Siu, L. Role of Topoisomerase II in Mediating Epipodophyllotoxin-Induced DNA Cleavage. Cancer Res. 1984, 44, 5857-5860.
23. You, Y. J.; Zheng, X. G.; Yong, R.; Ahn, B. Z. Naphthazarin derivatives: Synthesis, cytotoxic mechanism and evaluation of antitumor activity. Arch. Pharm. Res. 1998, 21, 595-598.
24. Fujii, N.; Yamashita, Y.; Arima, Y.; Nagashima, M.; Nakano, H. Induction of Topoisomerase II-Mediated DNA Cleavage by the Plant Naphthoquinones Plumbagin and Shikonin. Antimicrob. Agents Chemother. 1992, 36, 2589-2594.
25. Neder, K.; Marton, L. J.; Liu, L. F.; Frydman, B. Reaction of beta-lapachone and related naphthoquinones with 2-mercaptoethanol: A biomimetic model of topoisomerase II poisoning by quinones. Cell Mol. Biol. 1998, 44, 465-474.
26. Wang, H. K.; MorrisNatschke, S. L.; Lee, K. H. Recent advances in the discovery and development of topoisomerase inhibitors as antitumor agents. Med. Res. Rev. 1997, 17, 367-425.
27. Malonne, H.; Atassi, G. DNA topoisomerase targeting drugs: mechanisms of action and perspectives. Anti-Cancer Drug 1997, 8, 811-822.
28. Jensen, P. B.; Sehested, M. DNA topoisomerase II rescue by catalytic inhibitors - A new strategy to improve the antitumor selectivity of etoposide. Biochem. Pharmacol. 1997, 54, 755-759.
29. Ishida, R.; Miki, T.; Narita, T.; Yui, R.; Sato, M.; Utsumi, K. R.; Tanabe, K.; Andoh, T. Inhibition of Intracellular Topoisomerase II by Antitumor (2,6-dioxopiperazine) Derivatives: Mode of Cell Growth Inhibition Distinct from that of Cleavable Complex-Forming Type Inhibitors. Cancer Res. 1991, 51, 4909-4916.
30. Drake, F. H.; Hofmann, G. A.; Mong, S. M.; Bartus, J. O.; Hertzberg, R. P.; Johnson, R. K.; Mattern, M. R.; Mirabelli, C. K. In Vitro and Intracellular Inhibition of Topoisomerase II by the Antitumor Agent Mebarone. Cancer Res. 1989, 49, 2578-2583.
31. Andoh, T.; Ishida, R. Catalytic inhibitors of DNA topoisomerase II. Bba. Gene Struct. Express. 1998, 1400, 155-171.
32. Radisky, D. C.; Radisky, E. S.; Barrows, L. R.; Copp, B. R.; Kramer, R. A.; Ireland, C. M. Novel Cytotoxic Topoisomerase II Inhibiting Pyrroloiminoquinones from Fijian Sponges of the Genus Zyzzya. J. Am. Chem. Soc. 1993, 115, 1632-1638.
33. Venables, D. A.; Concepcion, G. P.; Matsumoto, S. S.; Barrows, L. R.; Ireland, C. M. Makaluvamine N: A new pyrroloiminoquinone from Zyzzya fuliginosa. J. Nat. Prod. 1997, 60, 408-410.
34. Höjeberg, B.; Blomberg, K.; Stenberg, S.; Lind, C. Biospecific Adsorption of Hepatic DT-Diaphorase on Immobilized Dicoumarol. Arch. Biochem. Biophys. 1981, 207, 205-216.
35. Alvarez, M.; Robey, R.; Sandor, V.; Nishiyama, K.; Matsumoto, Y.; Paull, K.; Bates, S.; Fojo, T. Using the national cancer institute anticancer drug screen to assess the effect of mrp expression on drug sensitivity profiles. Mol. Pharmacol. 1998, 54, 802-814.