CC-1065 and the duocarmycins: Recent developments

Expert Opinion on Therapeutic Patents

Volumn 10, Issue 12, 2000, Pages 1853-1871

  Cacciari, B ^a   Romagnoli, R ^a   Baraldi, P G ^a   Da Ros, T ^a   Spalluto, G ^a  

^a UNIVERSITY OF TRIESTE   (Italy)

Author keywords

Alkylating agents; Antitumour agents; CC 1065; DNA minor groove; Duocarmycins

Indexed keywords

1,2 DIHYDRO 3H PYRROLO[3,2 E]INDOLE; ADENINE; ADOZELESIN; ALKYLATING AGENT; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; BETA GLUCURONIDASE; BETA LACTAMASE; BIZELESIN; BLEOMYCIN A2; CARBAMIC ACID DERIVATIVE; CARZELESIN; CYCLOPROPANE; CYCLOPROPRROLOINDOLE DERIVATIVE; CYCLOPROPYLBEZENEINDOLE DERIVATIVE; DNA; DUOCARMYCIN A; DUOCARMYCIN SA; ESTERASE; GLYCOPEPTIDE; KW 285; MONOCLONAL ANTIBODY; PIBROZELESIN; PRODRUG; PYRROLOINDOLE DERIVATIVE; RACHELMYCIN; RACHELMYCIN DERIVATIVE; RNA; THIAMINE; U 71184; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; CANCER CELL CULTURE; CARCINOGENESIS; CONCENTRATION RESPONSE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CYTOTOXICITY; DNA ALKYLATION; DNA SEQUENCE; DRUG BINDING SITE; DRUG CONFORMATION; DRUG DNA BINDING; DRUG DNA INTERACTION; DRUG POTENCY; DRUG TARGETING; ELECTRONICS; GENE ACTIVATION; GENE EXPRESSION REGULATION; GENE MUTATION; HUMAN; HUMAN CELL; LEUKEMIA L 1210; LIVER METABOLISM; LIVER MITOCHONDRION; MOUSE; MUTATION; NONHUMAN; ONCOGENE; PATENT; REVIEW; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

EID: 0033664734     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.10.12.1853     Document Type: Review

References (96)

1. CC-1065 (NSC-298223) a new antitumor antibiotic. Production, in vitro biological activity, microbiological assays and taxonomy of the producing microorganism
2. Structure of CC-1065 (NSC 298223), a new antitumor antibiotic
3. CC-1065 (NSC 298223), a potent new antitumor agent improved production and isolation, characterization and antitumor activity
4. The structure of CC-1065, a potent antitumor agent and its binding to DNA
5. Duocarmycin A, a new antibiotic from Streptomyces
6. Structure of duocarmycins produced by Streptomyces sp
7. DC89-A1, a new antitumor antibiotic from Streptomyces
8. Pyrindamycins A and B, new antitumor antibiotics
9. New antitumor antibiotics, duocarmycins B1 and B2
10. Antitumor activity of pyrindamycins A and B
11. Duocarmycin SA, a new antitumor antibiotic from Streptomyces sp
12. Structure of duocarmycin SA, a potent antitumor antibiotic
13. Duocarmycins, new antitumor antibiotics produced by Streptomyces; producing organisms and improved production
14. Duocarmycins, potent antitumor antibiotics produced by Streptomyces sp. Structures and chemistry
15. CC-1065 and the duocarmycins: Unravelling the keys to a new class of naturally derived DNA alkylating
16. The duocarmycins: Synthetic and mechanistic studies
17. Duocarmycins: A new class of sequence selective DNA minor groove alkylating agents
18. Design, synthesis and evaluation of functional analogs of CC-1065 and the duocarmycins: A study of structural features effecting DNA binding selectivity
19. Dissecting the complex structure of CC-1065
20. Sequence selectivity of DNA covalent modification
21. Covalent binding of antitumor antibiotics in the minor groove of DNA. Mechanism of action of CC-1065 and the pyrrolo[1,4] benzodiazepines
22. The chemistry, mechanism of actions and biological properties of CC-1065, a potent antitumor antibiotic
23. CC-1065 Analogs: Sequence specific DNA-alkylating antitumor agents
24. 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
25. (+)- and ent-(-)-duocarmycin SA and (+)- and ent-(-)-N-Boc-DSA DNA alkylation properties. Alkylation site models that accommodate the offset AT-rich adenine N3 alkylation selectivity of enantiomeric agents
26. Synthesis and preliminary evaluation of agents incorporating the pharmacophore of the duocarmycin/pyrindamycin alkylation subunit: Identification of the CC-1065/duocarmycin common pharmacophore
27. Duocarmycin-pyrindamycin DNA alkylation properties and identifications, synthesis and evaluation of agents incorporating the pharmacophore of the CC-1065-duocarmycin common pharmacophore
28. Isolation and characyerization of duocarmycin-adenine DNA adduct
29. Reversibility of the duocarmycin-A and SA DNA alkylation reaction
30. DNA alkylation properties of the duocarmycin: (+)-duocarmycin A, Epi-(+)- duocarmycin A, Ent-(-)-duocarmycin A and Epi, Ent-(-)-duocarmycin A
31. Covalent alkylation of DNA with duocarmycin A. Identification if abasic site structure
32. A novel property of duocarmycin and its analogues for covalent reaction with DNA
33. A novel guanine N3 alkylation by antitumor antibiotic duocarmycin A
34. Concerted DNA recognition and novel site-specific alkylation by duocarmycin A with distamycin A
35. Reaction of the antitumor antibiotic CC-1065 with DNA: Structure of DNA adduct with DNA sequence specificity
36. Characterization of an adduct between CC-1065 and a defined oligodeoxynucleotide duplex
37. Reaction of the antitumor antibiotic CC-1065 with DNA. Location of the site of thermally induced strand breakage and analysis of DNA sequence specificity
38. Molecular basis for sequence-specific DNA alkylation by CC-1065
39. Sequence specificity of DNA alkylation by the unnatural enantiomer of CC-1065 and its synthetic analogues
40. Structure of the (+)-CC-1065-DNA adduct: Critical role of ordered water molecules and implications for involvement of phosphate catalysis in the covalent reaction
41. Reversibility of the covalent reaction of CC-1065 and analogues with DNA
42. 3. Preparation of key partial structures and definition of an additional functional role of central and right-hand subunits
43. 32P-end labeled double stranded DNA for binding studies: Development of a protocol for examination of functional features and the duocarmycins that contribute to their sequence-selective DNA alkylation properties
44. Demonstration and definition of the noncovalent binding selectivity of agents related to CC-1065 by an affinity cleavage agent: Noncovalent binding coincidental with alkylation
45. 2: Enhanced functional analogues of CC-1065 incorporating the 1,2,9,9a-tetrahydrocyclopropa [c]benz[e]indol-4-one (CBI) left hand subunit
46. CC-1065 and the Duocarmycins: Understanding their biological function through mechanistic studies
47. 1H NMR and restrained molecular dynamics simulation
48. Preliminary toxicity studies with the DNA-binding antibiotic, CC-1065
49. 2: Enhanced functional analogues of CC-10658 incorporating the 1, 2, 9, 9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) left hand subunit
50. 2; enhanced functional analogs of (+)-CC-1065. A critical appraisal of a proposed relationship between DNA binding properties and cytotoxic potency
51. (+)-CC-1065 DNA alkylation: Observation of an unexpected relationship between cyclopropane electrophile reactivity and the intensity of DNA alkylation
52. 2: An enhanced functional analog of (+)-CC1065
53. 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]in dol-4-one (MCBI) functional reactivity
54. Synthesis, chemical properties and preliminary evaluation of substituted CBI analogs of CC-1065 and the duocamycins incorporating the 7-cyano-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]-indol-4-one alkylation quantitation of the magnitude of electronic effects on functional reactivity
55. A Hammett correlation for CC-1065 and duocarmycin analogs-magnitude of substituent electronic effects on functional reactivity
56. Role of the CC-1065 and duocarmycin N2 substituent: Validation of a direct relationship between solvolysis chemical stability and in vitro biology potency
57. 1, 2, 9, 9a-Tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) analogs of CC-1065 and the duocarmycins: Synthesis and evaluation
58. 2CBI) alkylation subunit
59. Synthesis and evaluation of Cc-1065 and duocarmycin analogs incorporating the A-hexahydrocyclopropa[c]naphtho [2,1-b]azepin-6-one (CNA) alkylation subunit - Structural features that govern reactivity and reaction regioselectivity
60. Chemical and structural comparison of N- Boc-CBQ and N-Boc-CBI: Identification and structural origin of an unappreciated but productive of the CC-1065 and duocarmycin SA alkylation subunits
61. CC-1065 and the duocarmycins-synthetic studies
62. Are the duocarmycin and CC-1065 DNA alkylation reactions acid catalyzed? Solvolysis pH-rate profiles suggest they are not
63. 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
64. Synthesis, cytotoxicity, antitumor activity and sequence selective binding of two pyrazole analogs structurally related to the antitumor agents U- 71,184 and adozelesin
65. 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
66. Synthesis and evaluation of CC-1065 and duocarmycins analogues incorporating the iso-CI and iso-CBI alkylation subunits: Impact of relocation of the C4 carbonyl
67. Synthesis and evaluation of carbocyclic analogue of the CC-1065 and duocarmycin alkylation subunits: Role of the vinilogous amide and implications on DNA alkylation catalysis
68. Total synthesis and biological properties of novel antineoplastic (chloromethyl) furanoindolines: An asymmetric hydroboration mediated synthesis of the alkylation subunit
69. A novel phenol-forming reaction for preparation of benzene, furan and thiophene anlogs of CC- 1065/duocarmycins pharmacophore
70. Total synthesis of seco (+)- and ent-(-)-oxaduocarmycin SA: Construction of the (chloromethyl)indoline alkylating subunit by a novel intramolecular aryl radical cyclization onto a vinyl chloride
71. Synthesis of furan and thiophene analogs of duocarmycin SA
72. Heterocyclic analogs of DNA minor groove alkylating agents
73. Synthesis of CC-1065 and duocarmycin analogs via intramolecular aryl radical cyclization of a tethered vinyl chloride
74. A novel class of CC-1065 and duocarmycin analogues subject to mitomycin-related reductive activation
75. Selective metal cation activation of a DNA alkylating agent: Synthesis and evaluation of methyl 1, 2, 9, 9a-tetrahydrocyclo- propa[c] pyrido[3,2-e]indol-4-one-7-carboxylate (CPyI)
76. Synthesis and evaluation of 1, 2, 8, 8a-tetrahydrocyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one, the parent alkylation subunit substituents and its implications for DNA alkylation catalysis
77. Synthesis of 1-substituted 3-(chloromethyl)-6-aminoindoline (6-amino-seco-CI) minor groove alkylating agents and structure activity relationship for the cytotoxicity
78. Synthesis and cytotoxicity of 5-amino-1-(chloromethyl)3-[(5,6,7 -trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz[e]indole (amino-seco-CBI-TMI) and related 5- alkylamino analogues: New DNA minor groove alkylating agents
79. Synthesis and cytotoxicity of amino-seco-DSA: An amino analogue of the DNA alkylating agent duocarmycin SA
80. Stereoe-electronic factors influencing the biological activity and DNA interaction of synthesis antitumor agents modeled on CC-1065
81. Synthesis and biochemical evaluation of the CBI-PBE-I-dimer, a benzannelated analog of (+)-CC-1065 that also produces delayed toxicity in mice
82. Reserved and sandwiched analogs of duocarmycin SA: Establishment of the origin of the sequence-selective alkylation of DNA and new insights into the source of catalysis
83. CC-1065 analogs: An examples of enhancement of DNA alkylation efficiency through introduction of stabilizing electrostatic interactions
84. 1:CC-1065 analogs containing deep-seated modification in the DNA binding subunit
85. Critical role of the linking amide in CC-1065 and the duocarmycins: Implications on the source of DNA alkylation catalysis
86. Synthesis and evaluation of doucarmycin and CC-1065 analogues containing modifications in the subunit linking amide
87. Shape-dependent catalysis: Insight into the source of catalysis for the CC-1065 and duocarmycin DNA alkylation reaction
88. Bleomycin: Synthetic and mechanistic studies
89. Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing cinnamoyl groups
90. Synthesis and antitumor activity of duocarmycin derivatives: Modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups
91. A 2-nitroimidazole carbamate prodrug of 5-amino-1-(chloromethyl) -3-[{5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz [e]indole (amino-seco-CBI-TMI) for use with ADEPT and GDEPT
92. Evaluation of the antineoplastic activity of adozelesin alone and in combination with 5-aza-2'-deoxycytidine and cytosine arabinoside on DLD-1 human colon carcinoma cells
93. Adozelesin, a selected lead among cyclopropylpyrroloindole analogs of the DNA binding antibiotics, CC-1065
94. Cytotoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue
95. Preclinical pharmacology of bizelesin, a potent bifunctional analog of the DNA-binding antibiotic CC-1065
96. Characteristics of antitumor activity of KW-2189, a novel watersoluble derivative of duocarmycin, against murine and human tumors