Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products

Current Topics in Medicinal Chemistry

Volumn 9, Issue 16, 2009, Pages 1494-1524

  Ghosh, Nandita ^a   Sheldrake, Helen M ^a   Searcey, Mark ^b   Pors, Klaus ^a  

^a UNIVERSITY OF BRADFORD   (United Kingdom)

^b UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

Adenine N3 alkylation; Adozelesin; CBI; CC 1065; CPI; DNA minor groove binders (MGBs); Duocarmycin SA; Prodrugs

Indexed keywords

1,2,8,8A TETRAHYDROCYCLOPROPA[C]PYRAZOLO[4,3 E]INDOL 4 ONE DERIVATIVE; 1,2,8,8A TETRAHYDROCYCLOPROPA[C]PYRROLO[3,2 E]INDOL 4 ONE DERIVATIVE; 1,2,9,9A TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL 4 ONE DERIVATIVE; 1,2,9,9A TETRAHYDROCYCLOPROPA[C]PYRIDO[3,2 E]INDOL 4 ONE DERIVATIVE; ADENINE; ADOZELESIN; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; BIZELESIN; CARZELESIN; DOUBLE STRANDED DNA; DUOCARMYCIN B1; DUOCARMYCIN DERIVATIVE; PIBROZELESIN; RACHELMYCIN; UNCLASSIFIED DRUG; YATAKEMYCIN;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; BINDING SITE; BIOLOGICAL ACTIVITY; BONE MARROW SUPPRESSION; BREAST CANCER; CYTOTOXICITY; DNA ALKYLATION; DRUG CONJUGATION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HYPOXIA; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LIVER TOXICITY; MELANOMA; NONHUMAN; PHARMACOPHORE; REVIEW; SOLVOLYSIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS, ALKYLATING; BIOLOGICAL PRODUCTS; DRUG EVALUATION, PRECLINICAL; HUMANS; INDOLES; PYRROLIDINONES;

EID: 74249120351     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802609789909812     Document Type: Review

References (155)

1. Boger, D.L.; Boyce, C.W.; Garbaccio, R.M.; Goldberg, J.A. CC-1065 and the Duocarmycins: Synthetic Studies. Chem. Rev. 1997, 97, 787-828.
2. Boger, D.L.; Johnson, D.S. CC-1065 and the Duocarmycins: Understanding their biological function through mechanistic studies. Angew. Chem. Int. Ed. Engl. 1996, 35, 1438-1474.
3. Cacciari, B.; Romagnoli, R.; Baraldi, P.G.; Ros, T.D.; Spalluto, G. CC-1065 and the duocarmycins: recent developments. Expert Opin. Ther. Pat. 2000, 10, 1853-1871.
4. Igarashi, Y.; Futamata, K.; Fujita, T.; Sekine, A.; Senda, H.; Naoki, H.; Furumai, T. Yatakemycin, a novel antifungal antibiotic produced by Streptomyces sp. TP-A0356. J. Antibiot. (Tokyo) 2003, 56, 107-113.
5. Boger, D.L.; Ishizaki, T.; Zarrinmayeh, H. Isolation and characterisation of the duocarmycin-adenine DNA adduct. J. Am. Chem. Soc. 1991, 113, 6645-6649.
6. Eis, P.S.; Smith, J.A.; Rydzewski, J.M.; Case, D.A.; Boger, D.L.; Chazin, W.J. High resolution solution structure of a DNA duplex alkylated by the antitumor agent duocarmycin SA. J. Mol. Biol. 1997, 272, 237-252.
7. Wrasidlo, W.; Johnson, D.S.; Boger, D.L. Induction of endonucleocytic DNA fragmentation and apoptosis by the duocarmycins. Bioorg. Med. Chem. Lett. 1994, 4, 631-634.
8. McGovren, J.P.; Clarke, G.L.; Pratt, E.A.; DeKoning, T.F. Preliminary toxicity studies with the DNA-binding antibiotic, CC-1065. J. Antibiot. (Tokyo) 1984, 37, 63-70.
9. Krueger, W.C.; Prairie, M.D. Calf thymus DNA binding/bonding properties of CC-1065 and analogs as related to their biological activities and toxicities. Chem. Biol. Interact. 1992, 82, 31-46.
10. Ichimura, M.; Ogawa, T.; Takahashi, K.; Kobayashi, E.; Kawamoto, I.; Yasuzawa, T.; Takahashi, I.; Nakano, H. Duocarmycin SA, a new antitumor antibiotic from Streptomyces sp. J. Antibiot. (Tokyo) 1990, 43, 1037-1038.
11. Boger, D.L.; Garbaccio, R.M. Shape-dependent catalysis: Insights into the source of catalysis for the CC-1065 and duocarmycin DNA alkylation reaction. Acc. Chem. Res. 1999, 32, 1043-1052.
12. Wolkenberg, S.E.; Boger, D.L. Mechanisms of in situ activation for DNA-targeting antitumor agents. Chem. Rev. 2002, 102, 2477-2495.
13. Searcey, M. Duocarmycins - natures prodrugs? Curr. Pharm. Des. 2002, 8, 1375-1389.
14. Macmillan, K.S.; Boger, D.L. Fundamental Relationships between Structure, Reactivity, and Biological Activity for the Duocarmycins and CC-1065. J. Med. Chem. 2009. [Epub ahead of print]
15. Tichenor, M.S.; Boger, D.L. Yatakemycin: total synthesis, DNA alkylation, and biological properties. Nat. Prod. Rep. 2008, 25, 220-226.
16. Tichenor, M.S.; MacMillan, K.S.; Stover, J.S.; Wolkenberg, S.E.; Pavani, M.G.; Zanella, L.; Zaid, A.N.; Spalluto, G.; Rayl, T.J.; Hwang, I.; Baraldi, P.G.; Boger, D.L. Rational design, synthesis, and evaluation of key analogues of CC-1065 and the duocarmycins. J. Am. Chem. Soc. 2007, 129, 14092-14099.
17. Parrish, J.P.; Trzupek, J.D.; Hughes, T.V.; Hwang, I.; Boger, D.L. Synthesis and evaluation of N-aryl and N-alkenyl CBI derivatives. Bioorg. Med. Chem. 2004, 12, 5845-5856.
18. Parrish, J.P.; Hughes, T.V.; Hwang, I.; Boger, D.L. Establishing the parabolic relationship between reactivity and activity for derivatives and analogues of the duocarmycin and CC-1065 alkylation subunits. J. Am. Chem. Soc. 2004, 126, 80-81.
19. Sundberg, R.J.; Nishiguchi, T. Synthesis and intramolecular photoaddition of an indole quinonediazide. Tetrahedron Lett. 1983, 24, 4773-4776.
20. 32p-end-labeled double-stranded DNA for binding studies: Development of a protocol for examination of functional features of (+)-CC-1065 and the duocarmycins that contribute to their sequence-selective DNA alkylation properties. Tetrahedron 1991, 47, 2661-2682.
21. Tercel, M.; Denny, W.A. Synthesis of nitrogen and sulfur analogues of the seco-CI alkylating agent. J. Chem. Soc. Perkin Trans. 1 1998, 509-519.
22. Tercel, M.; Denny, W.A.; Wilson, W.R. Nitrogen and sulfur analogues of the secoCI alkylating agent: Synthesis and cytotoxicity. Bioorg. Med. Chem. Lett. 1996, 6, 2735-2740.
23. Milbank, J.B.; Tercel, M.; Atwell, G.J.; Wilson, W.R.; Hogg, A.; Denny, W.A. Synthesis of 1-substituted 3-(chloromethyl)-6-aminoindoline (6-amino-seco-CI) DNA minor groove alkylating agents and structure-activity relationships for their cytotoxicity. J. Med. Chem. 1999, 42, 649-658.
24. Tercel, M.; Gieseg, M.A.; Milbank, J.B.; Boyd, M.; Fan, J.Y.; Tan, L.K.; Wilson, W.R.; Denny, W.A. Cytotoxicity and DNA interaction of the enantiomers of 6-amino-3-(chloromethyl)-1-[(5,6,7-trimethoxyindol-2-yl)carbonyl]indo- line (amino-seco-CITMI). Chem. Res. Toxicol. 1999, 12, 700-706.
25. Kupchinsky, S.; Centioni, S.; Howard, T.; Trzupek, J.; Roller, S.; Carnahan, V.; Townes, H.; Purnell, B.; Price, C.; Handl, H.; Summerville, K.; Johnson, K.; Toth, J.; Hudson, S.; Kiakos, K.; Hartley, J.A.; Lee, M. A novel class of achiral seco-analogs of CC-1065 and the duocarmycins: design, synthesis, DNA binding, and anticancer properties. Bioorg. Med. Chem. 2004, 12, 6221-6236.
26. Toth, J.L.; Trzupek, J.D.; Flores, L.V.; Kiakos, K.; Hartley, J.A.; Pennington, W.T.; Lee, M. A novel achiral seco-amino-cyclopropylindoline (CI) analog of CC-1065 and the duocarmycins: design, synthesis and biological studies. Med. Chem. 2005, 1, 13-19.
27. Parrish, J.P.; Kastrinsky, D.B.; Stauffer, F.; Hedrick, M.P.; Hwang, I.; Boger, D.L. Establishment of substituent effects in the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065. Bioorg. Med. Chem. 2003, 11, 3815-3838.
28. Boger, D.L.; Schmitt, H.W.; Fink, B.E.; Hedrick, M.P. Parallel synthesis and evaluation of 132 (+)-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) analogues of CC-1065 and the duocarmycins defining the contribution of the DNA-binding domain. J. Org. Chem. 2001, 66, 6654-6661.
29. Boger, D.L.; Stauffer, F.; Hedrick, M.P. Substituent effects within the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065. Bioorg. Med. Chem. Lett. 2001, 11, 2021-2024.
30. Atwell, G.J.; Milbank, J.J.; Wilson, W.R.; Hogg, A.; Denny, W.A. 5-Amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles: relationships between structure and cytotoxicity for analogues bearing different DNA minor groove binding subunits. J. Med. Chem. 1999, 42, 3400-3411.
31. Boger, D.L.; Brunette, S.R.; Garbaccio, R.M. Synthesis and evaluation of a series of C3-substituted CBI analogues of CC-1065 and the duocarmycins. J. Org. Chem. 2001, 66, 5163-5173.
32. Boger, D.L.; Garbaccio, R.M.; Jin, Q. Synthesis and evaluation of CC-1065 and duocarmycin analogues incorporating the Iso-CI and Iso-CBI alkylation subunits: impact of relocation of the C-4 Carbony. J. Org. Chem. 1997, 62, 8875-8891.
33. Boger, D.L.; Turnbull, P. Synthesis and evaluation of a carbocyclic analogue of the CC-1065 and duocarmycin alkyla-tion subunits: role of the vinylogous amide and implications on DNA alkylation catalysis. J. Org. Chem. 1998, 63, 8004-8011.
34. Boger, D.L.; Boyce, C.W.; Garbaccio, R.M.; Searcey, M.; Jin, Q. CBI prodrug analogs of CC-1065 and the duocarmycins. Synthesis 1999, 1505-1509.
35. Boger, D.L.; Santillán, A.; Searcey, M.; Jin, Q. Critical role of the Linking amide in CC-1065 and the duocarmycins: implications on the source of DNA alkylation catalysis. J. Am. Chem. Soc. 1998, 120, 11554-11557.
36. Boger, D.L.; Garbaccio, R.M. Are the duocarmycin and CC-1065 DNA alkylation reactions acid-catalyzed? solvolysis pH-rate profiles suggest they are not. J. Org. Chem. 1999, 64, 5666-5669.
37. Kumar, R.; Lown, J.W. Design and synthesis of bis 1-chloromethyl-5- hydroxy-1,2- dihydro-3H-benz[e]indole (seco-CBI)-pyrrole polyamide conjugates. Org. Lett. 2002, 4, 1851-1854.
38. Reddy, B.S.; Sharma, S.K.; Lown, J.W. Recent developments in sequence selective minor groove DNA effectors. Curr. Med. Chem. 2001, 8, 475-508.
39. Denny, W.A. DNA minor groove alkylating agents. Curr. Med. Chem. 2001, 8, 533-544.
40. Wang, Y.; Yuan, H.; Ye, W.; Wright, S.C.; Wang, H.; Larrick, J.W. Synthesis and preliminary biological evaluations of CC-1065 analogues: effects of different linkers and terminal amides on biological activity. J. Med. Chem. 2000, 43, 1541-1549.
41. Atwell, G.J.; Tercel, M.; Boyd, M.; Wilson, W.R.; Denny, W.A. Synthesis and cytotoxicity of 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2yl) carbonyl]-1,2-dihydro-3H-benz[e]indole (amino-seco-CBI-TMI) and related 5-alkylamino analogues: new DNA minor groove alkylating agents. J. Org. Chem. 1998, 63, 9414-9420.
42. Boger, D.L.; Hughes, T.V.; Hedrick, M.P. Synthesis, chemical properties, and biological evaluation of CC-1065 and duocarmycin analogues incorporating the 5-methoxycarbonyl-1,2,9,9a-tetrahydrocyclopropa. J. Org. Chem. 2001, 66, 2207-2216.
43. Boger, D.L.; McKie, J.A.; Cai, H.; Cacciari, B.; Baraldi, P.G. Synthesis and properties of substituted CBI analogs of CC-1065 and the duocarmycins incorporating the 7-Methoxy-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (MCBI) alkylation subunit: magnitude of electronic effects on the functional reactivity. J. Org. Chem. 1996, 61, 1710-1729.
44. Boger, D.L.; Han, N.; Tarby, C.M.; Boyce, C.W.; Cai, H.; Jin, Q.; Kitos, P.A. Synthesis, chemical properties, and preliminary evaluation of substituted CBI analogs of CC-1065 and the duocarmycins incorporating the 7-cyano-1,2,9,9a-tetrahydrocyclopropa[ c]benz[e]indol-4-one alkylation subunit: hammett quantitation of the magnitude of electronic effects on functional reactivity. J. Org. Chem. 1996, 61, 4894-4912.
45. Yang, S.; Denny, W.A. A new short synthesis of 3-substituted 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indoles (amino-CBIs). J. Org. Chem. 2002, 67, 8958-8961.
46. Tercel, M.; Gieseg, M.A.; Denny, W.A.; Wilson, W.R. Synthesis and cytotoxicity of amino-seco-DSA: An amino analogue of the DNA alkylating agent Duocarmycin SA. J. Org. Chem. 1999, 64, 5946-5953.
47. Wang, Y.; Li, L.; Ye, W.; Tian, Z.; Jiang, W.; Wang, H.; Wright, S.C.; Larrick, J.W. CC-1065 analogues bearing different DNA-binding subunits: synthesis, antitumor activity, and preliminary toxicity study. J. Med. Chem. 2003, 46, 634-637.
48. Kiakos, K.; Sato, A.; Asao, T.; McHugh, P.J.; Lee, M.; Hartley, J.A. DNA sequence selective adenine alkylation, mechanism of adduct repair, and in vivo antitumor activity of the novel achiral seco-amino-cyclopropylbenz[e] indolone analogue of duocarmycin AS-I-145. Mol. Cancer Ther. 2007, 6, 2708-2718.
49. Boger, D.L.; Santillan, A., Jr.; Searcey, M.; Brunette, S.R.; Wolkenberg, S.E.; Hedrick, M.P.; Jin, Q. Synthesis and evaluation of 1,2,8, 8a-Tetrahydrocyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one, the parent alkylation subunit of CC-1065 and the duocarmycins: impact of the alkylation subunit substituents and its implications for DNA alkylation catalysis. J. Org. Chem. 2000, 65, 4101-4111.
50. Amishiro, N.; Okamoto, A.; Murakata, C.; Tamaoki, T.; Okabe, M.; Saito, H. Synthesis and antitumor activity of duocarmycin derivatives: modification of segment-A of A-ring pyrrole compounds. J. Med. Chem. 1999, 42, 2946-2960.
51. Nagamura, S.; Asai, A.; Amishiro, N.; Kobayashi, E.; Gomi, K.; Saito, H. Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing cinnamoyl groups. J. Med. Chem. 1997, 40, 972-979.
52. Amishiro, N.; Nagamura, S.; Kobayashi, E.; Okamoto, A.; Gomi, K.; Okabe, M.; Saito, H. Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing beta-(5′,6′,7′-trimethoxy- 2′-indolyl)acryloyl group. Bioorg. Med. Chem. 2000, 8, 1637-1643.
53. Amishiro, N.; Okamoto, A.; Okabe, M.; Saito, H. Synthesis and antitumor activity of duocarmycin derivatives: modification at the C-7 position of segment-A of A-ring pyrrole compounds. Bioorg. Med. Chem. 2000, 8, 1195-1201.
54. Amishiro, N.; Nagamura, S.; Murakata, C.; Okamoto, A.; Kobayashi, E.; Asada, M.; Gomi, K.; Tamaoki, T.; Okabe, M.; Yamaguchi, N.; Yamaguchi, K.; Saito, H. Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups. Bioorg. Med. Chem. 2000, 8, 381-391.
55. Mulay, I.L.; Roy, R.; Knox, B.E.; Suhr, N.H.; Delaney, W.E. Trace-metal analysis of cancerous and noncancerous human tissues. J. Natl. Cancer Inst. 1971, 47, 1-13.
56. Boger, D.L.; Boyce, C.W. Selective metal cation activation of a DNA alkylating agent: synthesis and evaluation of methyl 1,2,9, 9a- Tetrahydrocyclopropa[c]pyrido[3,2-e]indol-4-one-7-carboxylate (CPyI). J. Org. Chem. 2000, 65, 4088-4100.
57. Ellis, D.A.; Wolkenberg, S.E.; Boger, D.L. Metal cation complexation and activation of reversed CPyI analogues of CC-1065 and duocarmycin SA: partitioning the effects of binding and catalysis. J. Am. Chem. Soc. 2001, 123, 9299-9306.
58. Baraldi, P.G.; Cacciari, B.; Romagnoli, R.; Spalluto, G.; Boyce, C.W.; Boger, D.L. Resolution of a CPzI precursor, synthesis and biological evaluation of (+) and (-)-N-Boc-CPzI: a further validation of the relationship between chemical solvolytic stability and cytotoxicity. Bioorg. Med. Chem. Lett. 1999, 9, 3087-3092.
59. Baraldi, P.G.; Cacciari, B.; Pineda de las Infantas, M.J.; Romagnoli, R.; Spalluto, G.; Cozzi, P.; Mongelli, N. Synthesis, chemical solvolytic stability and preliminary biological evaluation of (+/-)-N-Boc-CPzI: a pyrazole analog of the left-hand segment of the antitumor agent CC-1065. Anticancer Drug Des. 1997, 12, 67-74.
60. Baraldi, P.G.; Cacciari, B.; Romagnoli, R.; Spalluto, G.; Gambari, R.; Bianchi, N.; Passadore, M.; Ambrosino, P.; Mongelli, N.; Cozzi, P.; Geroni, C. Synthesis, cytotoxicity, antitumor activity and sequence selective binding of two pyrazole analogs structurally related to the antitumor agents U-71,184 and adozelesin. Anticancer Drug Des. 1997, 12, 555-576.
61. Parrish, J.P.; Kastrinsky, D.B.; Hwang, I.; Boger, D.L. Synthesis and evaluation of duocarmycin and CC-1065 analogues incorporating the 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]-3-azaindol-4-one (CBA) alkylation subunit. J. Org. Chem. 2003, 68, 8984-8990.
62. Parrish, J.P.; Kastrinsky, D.B.; Boger, D.L. Synthesis and X-ray analysis of an unprecedented and stable 2-aza-4,4-spirocyclopropacyclohexadienone. Org. Lett. 2003, 5, 2577-2579.
63. Daniell, K.; Stewart, M.; Madsen, E.; Le, M.; Handl, H.; Brooks, N.; Kiakos, K.; Hartley, J.A.; Lee, M. Design, synthesis, and biological evaluation of achiral analogs of duocarmycin SA. Bioorg. Med. Chem. Lett. 2005, 15, 177-180.
64. Howard, T.T.; Lingerfelt, B.M.; Purnell, B.L.; Scott, A.E.; Price, C.A.; Townes, H.M.; McNulty, L.; Handl, H.L.; Summerville, K.; Hudson, S.J.; Bowen, J.P.; Kiakos, K.; Hartley, J.A.; Lee, M. Novel furano analogues of duocarmycin C1 and C2: design, synthesis, and biological evaluation of seco-iso- cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco- cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues. Bioorg. Med. Chem. 2002, 10, 2941-2952.
65. Boger, D.L.; Johnson, D.S.; Yun, W.; Tarby, C.M. Molecular basis for sequence selective DNA alkylation by (+)- and ent-(-)-CC-1065 and related agents: Alkylation site models that accommodate the offset AT-rich adenine N3 alkylation selectivity. Bioorg. Med. Chem. 1994, 2, 115-135.
66. Boger, D.L.; Searcey, M.; Tse, W.C.; Jin, Q. Bifunctional alkylating agents derived from duocarmycin SA: potent antitumor activity with altered sequence selectivity. Bioorg. Med. Chem. Lett. 2000, 10, 495-498.
67. Jia, G.; Lown, J.W. Design, synthesis and cytotoxicity evaluation of 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) dimers. Bioorg. Med. Chem. 2000, 8, 1607-1617.
68. Fukuda, Y.; Furuta, H.; Kusama, Y.; Ebisu, H.; Oomori, Y.; Terashima, S. The novel cyclopropapyrroloindole(CPI) bisalkylators bearing methoxycarbonyl and trifluoromethyl groups. Bioorg. Med. Chem. Lett. 1998, 8, 1387-1390.
69. Fukuda, Y.; Seto, S.; Furuta, H.; Ebisu, H.; Oomori, Y.; Terashima, S. The novel cyclopropapyrroloindole(CPI) bisalkylators bearing 3,3′-(1,4-phenylene)diacryloyl group as a linker. Bioorg. Med. Chem. Lett. 1998, 8, 2003-2004.
70. Fukuda, Y.; Seto, S.; Furuta, H.; Ebisu, H.; Oomori, Y.; Terashima, S. Novel seco cyclopropa[c]pyrrolo[3,2-e]indole bisalkylators bearing a 3,3′-arylenebisacryloyl group as a linker. J. Med. Chem. 2001, 44, 1396-1406.
71. Mehta, G.; Singh, V. Hybrid systems through natural product leads: An approach towards new molecular entities. Chem. Soc. Rev. 2002, 31, 324-334.
72. Baraldi, P.G.; Balboni, G.; Pavani, M.G.; Spalluto, G.; Tabrizi, M.A.; Clercq, E.D.; Balzarini, J.; Bando, T.; Sugiyama, H.; Romagnoli, R. Design, synthesis, DNA binding, and biological evaluation of water-soluble hybrid molecules containing two pyrazole analogues of the alkylating cyclopropylpyrroloindole (CPI) subunit of the antitumor agent CC-1065 and polypyrrole minor groove binders. J. Med. Chem. 2001, 44, 2536-2543.
73. Boger, D.L.; Han, N. CC-1065/duocarmycin and bleomycin A2 hybrid agents: lack of enhancement of DNA alkylation by attachment to noncomplementary DNA binding subunits. Bioorg. Med. Chem. 1997, 5, 233-243.
74. Fregeau, N.L.; Wang, Y.; Pon, R.T.; Wylie, W.A.; Lown, J.W. Characterization of a CPI-lexitropsin conjugate-oligonucleotide covalent complex by 'H NMR and restrained molecular dynamics simulation. J. Am. Chem. Soc. 1995, 117, 8917-8925.
75. Tao, Z.-F.; Saito, I.; Sugiyama, H. Highly co-operative DNA dialkylation by th ehomodimer of imidazole-pyrrole diamide-CPI conjugate with vinyl linker. J. Am. Chem. Soc. 2000, 122, 1602-1608.
76. Minoshima, M.; Bando, T.; Sasaki, S.; Shinohara, K.-i.; Shimizu, T.; Fujimoto, J.; Sugiyama, H. DNA alkylation by pyrroleimidazole seco-CBI conjugates with an indole linker: sequence specific DNA alkylation with 10-base-pair recognition through heterodimer formation. J. Am. Chem. Soc. 2007, 129, 5384-5390.
77. Bando, T.; Iida, H.; Tao, Z.-F.; Narita, A.; Fukuda, N.; Yamori, T.; Sugiyama, H. Sequence specificity, reactivity and antitumour activity of DNA alkylating pyrrole-imidazole diamides. Chem. Biol. 2003, 10, 751-758.
78. Jia, G.; Iida, h.; Lown, J.W. Synthesis of an unsymmetrical bis-lexitropsin-1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI) conjugate. Chem. Commun. 1999, 119-120.
79. Jia, G.; Lida, H.; Lown, J.W. Solid-phase synthesis of 1-chloromethyl-1,2-dihydro-3H-benz[e]indole (seco-CBI) and a polyamide conjugate. Synlett 2000, 603-606.
80. Kumar, R.; Lown, J.W. Synthesis and cytotoxicity evaluation of novel C7-c7, C7-N3 and N3-N3 dimers of 1-chloromethyl-5-hydroxy-1,2-dihydro-3H- benzo[e]indole (seco-CBI) with pyrrole and imidazole polyamide conjugates. Org. Biomol. Chem. 2003, 1, 2630-2647.
81. Sasaki, S.; Bando, T.; Minishima, M.; Shinohara, K.-i.; Sugiyama, H. Sequence-specific alkylation by Y-shaped and tandem hairpin pyrrole-imidazole polyamides. Chem. Eur. J. 2008, 14, 864-870.
82. Tao, Z.-F.; Fujiwara, T.; Saito, I.; Sugiyama, H. Rational design of sequence-specific DNA alkylating agents based on duocarmycin A and pyrrole-imidazole hairpin polyamides. J. Am. Chem. Soc. 1999, 121, 4961-4967.
83. Bando, T.; Narita, A.; Saito, H.; Sugiyama, H. Molecular design of apyrrole-imidazole hairpin polyamides for effective DNA alkylation. Chem. Eur. J. 2002, 8, 4781-4790.
84. Bando, T.; Narita, A.; Asada, K.; Ayame, H.; Sugiyama, H. Enantioselective DNA alkylation by a pyrrole-imidazole S-CBI conjugate. J. Am. Chem. Soc. 2004, 126, 8950-8955.
85. Bando, T.; Sugiyama, H. Synthesis and biological properties of sequence-specific DNA-alkylating pyrrole-imidazole polyamides. Acc. Chem. Res. 2006, 39, 935-944.
86. Oyoshi, T.; Kawakami, W.; Narita, A.; Bando, T.; Sugiyama, H. Inhibition of transcription at a coding sequence by alkylation polyamide. J. Am. Chem. Soc. 2003, 125, 4752.
87. Chang, A.Y.; Dervan, P.B. Strand selective cleavage of DNA by diastereomers of hairpin polyamide-seco-CBI conjugates. J. Am. Chem. Soc. 2000, 122, 4856-4864.
88. Shishido, K.; Haruna, S.; Yamamura, C.; Iitsuka, H.; Nemoto, H.; Shinohara, Y.; Shibuya, M. Synthesis and evaluation of the hybrid molecules possessing DNA-cleaving ability. Bioorg. Med. Chem. Lett. 1997, 7, 2617-2622.
89. Toth, J.L.; Price, C.A.; Madsen, E.C.; Handl, H.L.; Hudson, S.J.; Hubbard, R.B.I.; Bowen, J.P.; Kiakos, K.; Hartley, J.A.; Lee, M. Sequence selective recognition of dNA by hairpin conjugates of a racemic seco-cyclopropaneindoline-2-benzofurancarboxamide and polyamides. Bioorg. Med. Chem. Lett. 2002, 12, 2245-2248.
90. Price, C.A.; Lingerfelt, B.M.; Handl, H.A.; Kiakos, K.; Hartley, J.A.; Lee, M. Sequence specific recognition of DNA by tailor-made hairpin conjugates of achiral seco-cyclopropaneindoline- 2-benzofurancarboxamide and pyrrole-imidazole polyamides. Bioorg. Med. Chem. Lett. 2005, 15, 3151-3156.
91. Tao, Z.-F.; Fujiwara, T.; Saito, I.; Sugiyama, H. Sequence-specific DNA alkylation by hybrid molecules between Segment A of duocarmycin A and pyrrile/imidazole diamide. Angew. Chem. Int. Ed. 1999, 38, 650-653.
92. Yamamoto, K.; Sugiyama, H.; Kawanishi, S. Concerted DNA recognition and novel site-specific alkylation by duocarmycin A with distamycin A. Biochemistry 1993, 32, 1059-1066.
93. Fujiwara, T.; Tao, Z.-F.; Ozeki, Y.; Saito, I.; Wang, A.H.-J.; Lee, M.; Sugiyama, H. Modulation of sequence specificity of duocarmycin-dependent DNA alkylation by pyrrole-imidazole triamides. J. Am. Chem. Soc. 1999, 121, 7706-7707.
94. Bando, T.; Iida, H.; Saito, I.; Sugiyama, H. Sequence-specific DNA interstrand cross-linking by imidazole-pyrrole CPI conjugate. J. Am. Chem. Soc. 2001, 123, 5158-5159.
95. Bando, T.; Narita, A.; Saito, I.; Sugiyama, H. Highly Efficient Sequence-Specific DNA Interstrand Cross-Linking by Pyrrole/Imidazole CPI Conjugates. J. Am. Chem. Soc. 2003, 125, 3471-3485.
96. Suckling, C.J. Minor groove binders 1998 - 2004 Exp. Opin. Ther. Pat. 2004, 14, 1693-1724.
97. Zhou, Q.; Duan, W.; Simmons, D.; Shayo, Y.; Raymond, M.A.; Dorr, R.T.; Hurley, L.H. Design and Synthesis of a Novel DNA-DNA Interstrand Adenine-Guanine Cross-Linking Agent. J. Am. Chem. Soc. 2001, 123, 4865-4866.
98. Purnell, B.; Sato, A.; O'Kelley, A.; Price, C.; Summerville, K.; Hudson, S.; O'Hare, C.; Kiakos, K.; Asao, T.; Lee, M.; Hartley, J.A. DNA interstrand crosslinking agents: synthesis, DNA interactions, and cytotoxicity of dimeric achiral seco-amino-CBI and conjugates of achiral seco-amino-CBI with pyrrolobenzodiazepine (PBD). Bioorg. Med. Chem. Lett. 2006, 16, 5677-5681.
99. Burris, H.A.; Dieras, V.C.; Tunca, M.; Earhart, R.H.; Eckardt, J.R.; Rodriguez, G.I.; Shaffer, D.S.; Fields, S.M.; Campbell, E.; Schaaf, L.; Kasunic, D.; Von Hoff, D.D. Phase I study with the DNA sequence-specific agent adozelesin. Anticancer Drugs 1997, 8, 588-596.
100. Foster, B.J.; LoRusso, P.M.; Poplin, E.; Zalupski, M.; Valdivieso, M.; Wozniak, A.; Flaherty, L.; Kasunic, D.A.; Earhart, R.H.; Baker, L.H. Phase I trial of Adozelesin using the treatment schedule of daily x5 every 3 weeks. Invest. New Drugs 1996, 13, 321-326.
101. Fleming, G.F.; Ratain, M.J.; O'Brien, S.M.; Schilsky, R.L.; Hoffman, P.C.; Richards, J.M.; Vogelzang, N.J.; Kasunic, D.A.; Earhart, R.H. Phase I study of adozelesin administered by 24-hour continuous intravenous infusion. J. Natl. Cancer Inst. 1994, 86, 368-372.
102. Shamdas, G.J.; Alberts, D.S.; Modiano, M.; Wiggins, C.; Power, J.; Kasunic, D.A.; Elfring, G.L.; Earhart, R.H. Phase I study of adozelesin (U-73,975) in patients with solid tumors. Anticancer Drugs 1994, 5, 10-14.
103. Wolff, I.; Bench, K.; Beijnen, J.H.; Bruntsch, U.; Cavalli, F.; de Jong, J.; Groot, Y.; van Tellingen, O.; Wanders, J.; Sessa, C. Phase I clinical and pharmacokinetic study of carzelesin (U-80244) given daily for five consecutive days. Clin. Cancer Res. 1996, 2, 1717-1723.
104. Pitot, H.C.; Reid, J.M.; Sloan, J.A.; Ames, M.M.; Adjei, A.A.; Rubin, J.; Bagniewski, P.G.; Atherton, P.; Rayson, D.; Goldberg, R.M.; Erlichman, C. A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors. Clin. Cancer Res. 2002, 8, 712-717.
105. Schwartz, G.H.; Patnaik, A.; Hammond, L.A.; Rizzo, J.; Berg, K.; Von Hoff, D.D.; Rowinsky, E.K. A phase I study of bizelesin, a highly potent and selective DNA-interactive agent, in patients with advanced solid malignancies. Ann. Oncol. 2003, 14, 775-782.
106. Cristofanilli, M.; Bryan, W.J.; Miller, L.L.; Chang, A.Y.; Gradishar, W.J.; Kufe, D.W.; Hortobagyi, G.N. Phase II study of adozelesin in untreated metastatic breast cancer. Anticancer Drugs 1998, 9, 779-782.
107. Kinugawa, M.; Nagamura, S.; Sakaguchi, A.; Masuda, Y.; Saito, H.; Ogasa, T.; Kasai, M. Practical synthesis of the high-quality antitumor agent KW-2189 from duocarmycin B2 using a facile one-pot synthesis of an intermediate. Org. Proc. Res. Dev. 1998, 2, 344-350.
108. Asai, A.; Nagamura, S.; Saito, H. A Novel Property of Duocarmycin and Its Analogues for Covalent Reaction with DNA. J. Am. Chem. Soc. 1994, 116, 4171-4177.
109. Nagamura, S.; Asai, A.; Kanda, Y.; Kobayashi, E.; Gomi, K.; Saito, H. Synthesis and antitumor activity of duocarmycin derivatives: modification of segment A of duocarmycin B2. Chem. Pharm. Bull. (Tokyo) 1996, 44, 1723-1730.
110. Kobayashi, E.; Okamoto, A.; Asada, M.; Okabe, M.; Nagamura, S.; Asai, A.; Saito, H.; Gomi, K.; Hirata, T. Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors. Cancer Res. 1994, 54, 2404-2410.
111. Ogasawara, H.; Nishio, K.; Takeda, Y.; Ohmori, T.; Kubota, N.; Funayama, Y.; Ohira, T.; Kuraishi, Y.; Isogai, Y.; Saijo, N. A novel antitumor antibiotic, KW-2189 is activated by carboxyl esterase and induces DNA strand breaks in human small cell lung cancer cells. Jpn. J. Cancer Res. 1994, 85, 418-425.
112. Markovic, S.N.; Suman, V.J.; Vukov, A.M.; Fitch, T.R.; Hillman, D.W.; Adjei, A.A.; Alberts, S.R.; Kaur, J.S.; Braich, T.A.; Leitch, J.M.; Creagan, E.T. Phase II trial of KW2189 in patients with advanced malignant melanoma. Am. J. Clin. Oncol. 2002, 25, 308-312.
113. Small, E.J.; Figlin, R.; Petrylak, D.; Vaughn, D.J.; Sartor, O.; Horak, I.; Pincus, R.; Kremer, A.; Bowden, C. A phase II pilot study of KW-2189 in patients with advanced renal cell carcinoma. Invest. New Drugs 2000, 18, 193-197.
114. Alberts, S.R.; Suman, V.J.; Pitot, H.C.; Camoriano, J.K.; Rubin, J. Use of KW-2189, a DNA minor groove-binding agent, in patients with hepatocellular carcinoma: a north central cancer treatment group (NCCTG) phase II clinical trial. J. Gastrointest. Cancer 2008, 38, 10-14.
115. Xu, G.; McLeod, H.L. Strategies for enzyme/prodrug cancer therapy. Clin. Cancer Res. 2001, 7, 3314-3324.
116. Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.; Jarvinen, T.; Savolainen, J. Prodrugs: design and clinical applications. Nat. Rev. Drug Discov. 2008, 7, 255-270.
117. Groot, F.M.H.; Damen, E.W.P.; Scheeren, H.W. Anticancer prodrugs for application in monotherapy: targeting hypoxia, tumor-associated enzymes, and receptors. Curr. Med. Chem. 2001, 8, 1093-1122.
118. Sperker, B.; Backman, J.T.; Kroemer, H.K. The role of β-glucuronidase in drug disposition and drug targeting in humans. Clin. Pharmacokinet. 1997, 33, 18-31.
119. Tietze, L.F.; Schuster, H.J.; Schmuck, K.; Schuberth, I.; Alves, F. Duocarmycin-based prodrugs for cancer monotherapy. Bioorg. Med. Chem. 2008, 16, 6312-6318.
120. Yvon, A.M.; Wadsworth, P.; Jordan, M.A. Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol. Biol. Cell. 1999, 10, 947-959.
121. Wang, Y.; Li, L.; Jiang, W.; Larrick, J.W. Synthesis and evaluation of a DHA and 10-hydroxy camptothecin conjugate. Bioorg. Med. Chem. 2005, 13, 5592-5599.
122. Wang, Y.; Li, L.; Tian, Z.; Jiang, W.; Larrick, J.W. Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 2006, 14, 7854-7861.
123. Amishiro, N.; Nagamura, S.; Kobayashi, E.; Gomi, K.; Saito, H. New water-soluble duocarmycin derivatives: synthesis and antitumor activity of A-ring pyrrole compounds bearing beta-heteroarylacryloyl groups. J. Med. Chem. 1999, 42, 669-676.
124. Asai, A.; Nagamura, S.; Kobayashi, E.; Gomi, K.; Saito, H. Synthesis and antitumor activity of water-soluble duocarmycin B1 prodrugs. Bioorg. Med. Chem. Lett. 1999, 9, 2995-2998.
125. Rak, J.W.; St Croix, B.D.; Kerbel, R.S. Consequences of angiogenesis for tumor progression, metastasis and cancer therapy. Anticancer Drugs 1995, 6, 3-18.
126. Tomida, A.; Tsuruo, T. Drug resistance mediated by cellular stress response to the microenvironment of solid tumors. Anticancer Drug Des. 1999, 14, 169-177.
127. Brown, J.M. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Mol. Med. Today 2000, 6, 157-162.
128. Jin, W.; Trzupek, J.D.; Rayl, T.J.; Broward, M.A.; Vielhauer, G.A.; Weir, S.J.; Hwang, I.; Boger, D.L. A unique class of duocarmycin and CC-1065 analogues subject to reductive activation. J. Am. Chem. Soc. 2007, 129, 15391-15397.
129. Boger, D.L.; Garbaccio, R.M. A novel class of CC-1065 and duocarmycin analogues subject to mitomycin-related reductive activation. J. Org. Chem. 1999, 64, 8350-8362.
130. Knox, R.J. Overview: Gene-directed enzyme prodrug therapy (GDEPT) - recognising the present limitationso f gene therapy for the treatment of cancer. Curr. Opin. Invest. Drugs 2001, 2, 835-838.
131. Denny, W.A. Nitroreductase-based GDEPT. Curr. Pharm. Des. 2002, 8, 1349-1361.
132. Hay, M.P.; Anderson, R.F.; Ferry, D.M.; Wilson, W.R.; Denny, W.A. Synthesis and evaluation of nitroheterocyclic carbamate prodrugs for use with nitroreductase-mediated gene-directed enzyme prodrug therapy. J. Med. Chem. 2003, 46, 5533-5545.
133. Hay, M.P.; Sykes, B.M.; Denny, W.A.; Wilson, W.R. A 2-nitroimidazole carbamate prodrug of 5-amimo-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl) carbony l]-1,2-dihydro-3H-benz[E] indole (amino-seco-CBI-TMI) for use with ADEPT and GDEPT. Bioorg. Med. Chem. Lett. 1999, 9, 2237-2242.
134. Hay, M.P.; Atwell, G.J.; Wilson, W.R.; Pullen, S.M.; Denny, W.A. Structure-activity relationships for 4-nitrobenzyl carbamates of 5-aminobenz[e]indoline minor groove alkylating agents as prodrugs for GDEPT in conjunction with E. coli nitroreductase. J. Med. Chem. 2003, 46, 2456-2466.
135. Tietze, L.F.; Lieb, M.; Herzig, T.; Haunert, F.; Schuberth, I. A strategy for tumor-selective chemotherapy by enzymatic liberation of seco-duocarmycin SA-derivatives from nontoxic prodrugs. Bioorg. Med. Chem. 2001, 9, 1929-1939.
136. Tietze, L.F.; Feuerstein, T. Highly selective compounds for the antibody-directed enzyme prodrug therapy of cancer. Aust. J. Chem. 2003, 56, 841-854.
137. Tietze, L.F.; Major, F. Synthesis of new water-soluble DNA-binding subunits for analogues of the cytotoxic antibiotic CC-1065 and their prodrugs. Eur. J. Org. Chem. 2006, 2314-2321.
138. Tietze, L.F.; Major, F.; Schuberth, I. Antitumor agents: development of highly potent glycosidic duocarmycin analogues for selective cancer therapy. Angew. Chem. Int. Ed. 2006, 45, 6574-6577.
139. Tietze, L.F.; Panknin, O.; Major, F.; Krewer, B. Synthesis of a novel pentagastrin-drug conjugate for a targeted tumor therapy. Chemistry 2008, 14, 2811-2818.
140. Tietze, L.F.; von Hof, J.M.; Krewer, B.; Mueller, M.; Major, F.; Schuster, H.J.; Schoberth, I.; Alves, F. Asymmetric synthesis and biological evaluation of glycosidic prodrugs for a selective cancer therapy. Chemmedchem 2008, 3, 1946-1955.
141. Tietze, L.F.; Schuster, H.J.; Krewer, B.; Schuberth, I. Synthesis and biological studies of different duocarmycin based glycosidic prodrugs for their use in the antibody-directed enzyme prodrug therapy. J. Med. Chem. 2009, 52, 537-543.
142. Tietze, L.F.; Krewer, B. Novel analogues of CC-1065 and the duocarmycins for the use in targeted tumour therapies. Anticancer Agents Med. Chem. 2009, 9, 304-325.
143. Tietze, L.F.; Herzig, T.; Fecher, A.; Haunert, F.; Schuberth, I. Highly selective glycosylated prodrugs of cytostatic CC-1065 analogues for antibody-directed enzyme tumor therapy. Chembiochem 2001, 2, 758-765.
144. Tietze, L.F.; Feuerstein, T.; Fecher, A.; Haunert, F.; Panknin, O.; Borchers, U.; Schuberth, I.; Alves, F. Proof of principle in the selective treatment of cancer by antibody-directed enzyme prodrug therapy: the development of a highly potent prodrug. Angew. Chem. Int. Ed. 2002, 41, 759-761.
145. Tietze, L.F.; Major, F.; Schuberth, I.; Spiegl, D.A.; Krewer, B.; Maksimenka, K.; Bringmann, G.; Magull, J. Selective treatment of cancer: synthesis, biological evaluation and structural elucidation of novel analogues of the antibiotic CC-1065 and the duocarmycins. Chem. Eur. J. 2007, 13, 4396-4409.
146. Tietze, L.F.; Schuster, H.J.; Hampel, S.M.; Ruhl, S.; Pfoh, R. Enantio- and diastereoselective synthesis of duocarmycine-based prodrugs for a selective treatment of cancer by epoxide opening. Chem. Eur. J. 2008, 14, 895-901.
147. Wang, Y.; Yuan, H.; Wright, S.C.; Wang, H.; Larrick, J.W. Synthesis and preliminary cytotoxicity study of a cephalosporin-CC-1065 analogue prodrug. BMC Chem. Biol. 2001, 1, 4.
148. Wang, Y.; Yuan, H.; Wright, S.C.; Wang, H.; Larrick, J.W. Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues. Bioorg. Med. Chem. 2003, 11, 1569-1575.
149. Lambert, J.M. Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr. Opin. Pharmacol. 2005, 5, 543-549.
150. Chari, R.V.; Jackel, K.A.; Bourret, L.A.; Derr, S.M.; Tadayoni, B.M.; Mattocks, K.M.; Shah, S.A.; Liu, C.; Blattler, W.A.; Goldmacher, V.S. Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. Cancer Res. 1995, 55, 4079-4084.
151. Suzawa, T.; Nagamura, S.; Saiot, H.; Ohta, S.; Hanai, N.; Yamasaki, M. Synthesis and HPLC analysis of enzymatically cleavable linker consisting of poly(ethylene glycol) and dipeptide for the development of immunoconjugate. J. Control. Release 2000, 69, 27-41.
152. Suzawa, T.; Nagamura, S.; Saito, H.; Ohta, S.; Hanai, N.; Yamasaki, M. Synthesis of a novel duocarmycin derivative DU-257 and its application to immunoconjugate using poly(ethylene glycol)-dipeptidyl linker capable of tumor specific activation. Bioorg. Med. Chem. 2000, 8, 2175-2184.
153. Jeffrey, S.C.; Torgov, M.Y.; Andreyka, J.B.; Boddington, L.; Cerveny, C.G.; Denny, W.A.; Gordon, K.A.; Gustin, D.; Haugen, J.; Kline, T.; Nguyen, M.T.; Senter, P.D. Design, synthesis and in vitro evaluation of dipeptide-based antibody minor groove binder conjugates. J. Med. Chem. 2005, 48, 1344-1358.
154. Wang, Y.; Jiang, J.; Jiang, X.; Cai, S.; Han, H.; Li, L.; Tian, Z.; Jiang, W.; Zhang, Z.; Xiao, Y.; Wright, S.C.; Larrick, J.W. Synthesis and antitumour activity evaluations of albumin-binding prodrugs of CC-1065 analog. Bioorg. Med. Chem. 2008, 16, 6552-6559.
155. Kratz, F.; Beyer, U. Serum proteins as drug carriers: a review. Drug Deliv. 1998, 5, 281-299.