Double-strand DNA cleavage by copper·prodigiosin [24]

Journal of the American Chemical Society

Volumn 122, Issue 26, 2000, Pages 6333-6334

  Melvin, Matt S ^a   Tomlinson, John T ^a   Saluta, Gilda R ^b   Kucera, Gregory L ^b   Lindquist, Neils ^c   Manderville, Richard A ^a  

^a WAKE FOREST UNIVERSITY   (United States)

^b WAKE FOREST SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER; DOUBLE STRANDED DNA; PRODIGIOSIN;

CONTROLLED STUDY; CYTOTOXICITY; DNA CLEAVAGE; DRUG INHIBITION; DRUG POTENCY; HUMAN; HUMAN CELL; LETTER; OXIDATION REDUCTION REACTION;

EID: 0034608924     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0000798     Document Type: Letter

References (49)

1. Prodigiosin (1) was a gift from the Natural Products Division of the National Cancer Institute (NCI) and was received as a dark red powder.
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5. For synthesis see: (a) Wasserman, H. H.; McKeon, J. E.; Smith, L.; Forgione, P. J. Am. Chem. Soc. 1960, 82, 506. (b) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635. (c) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro, J. J. Org. Chem. 1970, 35, 142. (d) Boger, D. L.; Patel, M. Tetrahedron Lett. 1987, 28, 2499. (e) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989, 1725 (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (g) Fürstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (i) Fürster, A.; Grahowski, J.; Lehmann, C. W. J. Org. Chem. 1999, 64, 8275. (j) Fürstner, A.; Krause, H. J. Org. Chem. 1999, 64, 8281.
6. For synthesis see: (a) Wasserman, H. H.; McKeon, J. E.; Smith, L.; Forgione, P. J. Am. Chem. Soc. 1960, 82, 506. (b) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635. (c) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro, J. J. Org. Chem. 1970, 35, 142. (d) Boger, D. L.; Patel, M. Tetrahedron Lett. 1987, 28, 2499. (e) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989, 1725 (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (g) Fürstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (i) Fürster, A.; Grahowski, J.; Lehmann, C. W. J. Org. Chem. 1999, 64, 8275. (j) Fürstner, A.; Krause, H. J. Org. Chem. 1999, 64, 8281.
7. For synthesis see: (a) Wasserman, H. H.; McKeon, J. E.; Smith, L.; Forgione, P. J. Am. Chem. Soc. 1960, 82, 506. (b) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635. (c) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro, J. J. Org. Chem. 1970, 35, 142. (d) Boger, D. L.; Patel, M. Tetrahedron Lett. 1987, 28, 2499. (e) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989, 1725 (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (g) Fürstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (i) Fürster, A.; Grahowski, J.; Lehmann, C. W. J. Org. Chem. 1999, 64, 8275. (j) Fürstner, A.; Krause, H. J. Org. Chem. 1999, 64, 8281.
8. For synthesis see: (a) Wasserman, H. H.; McKeon, J. E.; Smith, L.; Forgione, P. J. Am. Chem. Soc. 1960, 82, 506. (b) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635. (c) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro, J. J. Org. Chem. 1970, 35, 142. (d) Boger, D. L.; Patel, M. Tetrahedron Lett. 1987, 28, 2499. (e) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989, 1725 (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (g) Fürstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (i) Fürster, A.; Grahowski, J.; Lehmann, C. W. J. Org. Chem. 1999, 64, 8275. (j) Fürstner, A.; Krause, H. J. Org. Chem. 1999, 64, 8281.
9. For synthesis see: (a) Wasserman, H. H.; McKeon, J. E.; Smith, L.; Forgione, P. J. Am. Chem. Soc. 1960, 82, 506. (b) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635. (c) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro, J. J. Org. Chem. 1970, 35, 142. (d) Boger, D. L.; Patel, M. Tetrahedron Lett. 1987, 28, 2499. (e) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989, 1725 (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (g) Fürstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (i) Fürster, A.; Grahowski, J.; Lehmann, C. W. J. Org. Chem. 1999, 64, 8275. (j) Fürstner, A.; Krause, H. J. Org. Chem. 1999, 64, 8281.
10. For synthesis see: (a) Wasserman, H. H.; McKeon, J. E.; Smith, L.; Forgione, P. J. Am. Chem. Soc. 1960, 82, 506. (b) Rapoport, H.; Holden, K. G. J. Am. Chem. Soc. 1962, 84, 635. (c) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro, J. J. Org. Chem. 1970, 35, 142. (d) Boger, D. L.; Patel, M. Tetrahedron Lett. 1987, 28, 2499. (e) Wasserman, H. H.; Lombardo, L. J. Tetrahedron Lett. 1989, 1725 (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (g) Fürstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305. (f) D'Alessio, R.; Rossi, A. Synlett 1996, 513. (i) Fürster, A.; Grahowski, J.; Lehmann, C. W. J. Org. Chem. 1999, 64, 8275. (j) Fürstner, A.; Krause, H. J. Org. Chem. 1999, 64, 8281.
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45. Gels were quantified using a Microtek Scanmaker E6 and the software program NIH Image 1.59. The amount of supercoiled plasmid DNA (Form I) was multiplied by a factor of 1.22 to account for reduced ethidium bromide intercalation into the supercoiled DNA.
46. 1), where h is the maximum separation in base pairs between two cuts on complementary strands that produces a linear DNA molecule (h = 16) and L is the number of phosphoester bonds per DNA strand in the plasmid (L = 2663).
47. Reactions of CuProd (10-50 μM) with Form I DNA were carried out at 37°C in 10 mM MOPS buffer, pH 7.4, and were quenched by addition of loading buffer after the required reaction time. The percent of Forms 1, II. and III was quantified and first-order rate constants were determined using the ENZFITTER program. Average errors in rate constants were ±20%.
48. The synthetic analogues 3 and 4 were prepared from 5-ethyl-1H-pyrrole-2-carboxaldehyde using a procedure similar to that described by Rossi for other prodigiosin analogues (ref 3f). Full experimental details are provided in the Supporting Information.
49. Clonogenic survival assays were used to assess the cytotoxicity of prodigiosin (1) and the synthetic analogues 3 and 4 in HL-60, a model of human promyelocytic leukemia, cancer cells. Details are provided in the Supporting Information.