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Nonintercalative DNA-binding antitumour compounds

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Summary

A family of compounds which appear to bind reversibly to double stranded DNA without intercalation between DNA base pairs has been defined. Methods are described by which this non-intercalative binding can be characterised using ultraviolet spectrometry, fluorimetry with ethidium as a probe, viscometry and other hydrodynamic techniques, circular dichroism and nuclear magnetic resonance spectrometry. Antibiotics which fall into this family include the antibiotics distamycin A, netropsin, mithramycin, chromomycin and olivomycin. Synthetic antitumour agents include diarylamidines such as berenil, phthalanilides, aromatic bisguanylhydrazones and bisquaternary ammonium heterocycles. A survey has been made of the general requirements of this family of compounds for DNA binding and biological activity. Binding of drugs to the minor groove of the DNA double helix appears to be the most likely mechanism for the antitumour action of these compounds.

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References

  1. Zimmer, C., 1975. Prog. Nucleic Acid Res. Mol. Biol. 15: 285–318.

    Google Scholar 

  2. Braithwaite, A. W. & Baguley, B. C., 1980. Biochemistry 19: 1101–1106.

    Google Scholar 

  3. Waring, M. J., 1965. J. Mol. Biol. 13: 269–282.

    Google Scholar 

  4. Sobell, H. M., Tsai, C.-C., Jain, S. C. & Gilbert, S. G., 1977. J. Mol. Biol. 114: 333–365.

    Google Scholar 

  5. Blake, A. & Peacocke, A. R., 1968. Biopolymers 6: 1225–1253.

    Google Scholar 

  6. Müller, W. & Gautier, 1978. Eur. J. Biochem. 54: 385–394.

    Google Scholar 

  7. Müller, W., Crothers, D. M. & Waring, M. J., 1973. Eur. J. Biochem. 39: 223–234.

    Google Scholar 

  8. Le Pecq, J.-B. & Paoletti, C., 1967. J. Mol. Biol. 27: 87–106.

    Google Scholar 

  9. Hahn, F. E., 1975. In: Antibiotics—III. Mechanism of Action of Antimicrobial and Antitumor Agents (Corcoran, J. W. & Hahn, F. E. eds), pp. 79–100, Springer Verlag, Berlin.

  10. Baguley, B. C. & Falkenhaug, E.-M., 1978. Nucleic Acids Res. 5: 161–171.

    Google Scholar 

  11. Cain, B. F., Baguley, B. C. & Denny, W. A., 1978. J. Med. Chem. 21: 658–668.

    Google Scholar 

  12. Baguley, B. C., Denny, W. A., Atwell, G. J. & Cain, B. F., 1981. J. Med. Chem. 24: 170–177.

    Google Scholar 

  13. McGhee, J. D. & von Hippel, P. H., 1974. J. Mol. Biol. 86: 469–489.

    Google Scholar 

  14. Arnett, S., Bond, P. J. & Chandrasekaram, R., 1980. Nature 287: 561–563.

    Google Scholar 

  15. Waring, M. J., 1981. Ann. Rev. Biochem. 50: 159–192.

    Google Scholar 

  16. Bauer, W. R., 1978. Ann. Rev. Biophys. Bioeng. 7: 287–331.

    Google Scholar 

  17. Revet, B. M., Schmir, M. & Vinograd, J., 1971. Nature (London), New Biol. 229: 10–13.

    Google Scholar 

  18. Dalgleish, D. G., Feil, M. C. & Peacocke, A. R., 1972. Biopolymers 11: 2415–2422.

    Google Scholar 

  19. Dalgleish, D. G., Peacocke, A. R., Fey, G. & Harve, G., 1971. Biopolymers 10: 1853–1863.

    Google Scholar 

  20. Dalgleish, D. G., Fey, G. & Kersten, H., 1974. Biopolymers 13: 1757–1766.

    Google Scholar 

  21. Zimmer, C., 1980. Biochim. Biophys. Acta 607: 232–246.

    Google Scholar 

  22. Michenkova, L. & Zimmer, C., 1980. Biopolymers 19: 823–831.

    Google Scholar 

  23. Patel, D. J., 1979. Accounts Chem. Res. 12: 118–125.

    Google Scholar 

  24. Phillips, D. R. & Roberts, G. C. K., 1980. Biochemistry 19: 4795–4801.

    Google Scholar 

  25. Patel, D. J. & Canuel, L. L., 1977. Proc. Natl. Acad. Sci. U.S.A. 74: 5207–5211.

    Google Scholar 

  26. Patel, D. J. & Canuel, L. L., 1979. Proc. Natl. Acad. Sci. U.S.A. 76: 24–28.

    Google Scholar 

  27. Patel, D., 1980. In: Nucleic Acid Geometry and Dynamics, (Sarma, R. H., ed), pp. 185–231, Permagon Press, New York.

  28. Hahn, F. E., 1980. Antibiot. Chemother. 27: 70–92.

    Google Scholar 

  29. Krey, A. K., 1980. Prog. Mol. Subcell. Biol. 7: 43–87.

    Google Scholar 

  30. Bialer, M., Yagen, B., Mechoulam, R. & Becker, Y., 1980. J. Med. Chem. 23: 1144–1148.

    Google Scholar 

  31. Berman, H. M., Neidle, S., Zimmer, C. & Thrum, H., 1979. Biochim. Biophys. Acta 561: 124–131.

    Google Scholar 

  32. Gurskaya, G. V., Grokhovsky, S. L., Zhuze, A. L. & Gottikh, B. P., 1979. Biochim. Biophys. Acta 563: 336–342.

    Google Scholar 

  33. Mackenzie, A. R., 1966. Cancer 19: 1369–1376.

    Google Scholar 

  34. Slavic, M. & Carter, S. K., 1975. Adv. Pharmacol. Chemother. 12: 1–30.

    Google Scholar 

  35. Gause, G. F., 1975. In: Antibiotics—III. Mechanism of Action of Antimicrobial and Antitumor Agents (Corcoran, J. W. & Hahn, F. E., eds), pp. 197–202, Springer Verlag, Berlin.

  36. Kersten, H. & Kersten, W., 1974. In: Inhibitors of Nucleic Acid Synthesis: Biophysical and Biochemical Aspects. Molecular Biology, Biochemistry and Biophysics (Kleinzeller, A., Springer, G. F. & Wittman, H. G. eds), vol. 18, pp. 86–96, Springer Verlag, Berlin.

  37. Behr, W., Honikel, K. & Hartmann, G., 1969. Eur. J. Biochem. 9: 82–92.

    Google Scholar 

  38. Waring, M. J., 1971. Prog. Mol. Subcell. Biol. 2: 215–229.

    Google Scholar 

  39. Ward, D., Reich, E. & Goldberg, I. H., 1965. Science 149: 1259–1273.

    Google Scholar 

  40. Kumar, V., Remers, W. A. & Bradner, W. T., 1980. J. Med. Chem. 23: 376–379.

    Google Scholar 

  41. Newton, B. A., 1975. In: Antibiotics—III. Mechanism of Action of Antimicrobial and Antitumor Agents (Corcoran, J. W. & Hahn, F. E. eds), pp. 34–47, Springer Verlag, Berlin.

  42. Cain, B. F., Atwell, G. J. & Seelye, R. N., 1969. J. Med. Chem. 12: 199–206.

    Google Scholar 

  43. Snapper, I., 1948. J. Am. Med. Ass. 137: 513–516.

    Google Scholar 

  44. Jensch, H., 1958. Med. Chem. 6: 134–169.

    Google Scholar 

  45. Bennett, L. L. Jr., 1965. Prog. Exp. Tumor Res. 7: 259–325.

    Google Scholar 

  46. Anné, J., De Clerq, E., Eyssen, H. & Dann, O., 1980. Antimicrob. Agents Chemother. 18: 231–239.

    Google Scholar 

  47. De Clerq, E. & Dann, O., 1980. J. Med. Chem. 23: 787–795.

    Google Scholar 

  48. Hirt, R. & Berchtold, R., 1969. Experientia 17: 418–420.

    Google Scholar 

  49. Yesair, D. W. & Kensler, C. J., 1975. In: Handbook of Experimental Pharmacology: Antineoplastic and Immunesuppressive Agents (Brodie, B. B. & Gillette, J. R., eds), vol 38, part 2, pp. 820–828, Springer Verlag, Berlin.

  50. Sivak, A., Rogers, W. I., Wodinsky, I. & Kensler, C. J., 1965. Cancer Res. 25: 902–909.

    Google Scholar 

  51. Rauen, H. M., Norpoth, K., Unterberg, W. & Haar, H., 1965. Experientia 21: 300–304.

    Google Scholar 

  52. Yesair, D. W., Kohner, F. A., Rogers, W. I., Baronwsky, P. E. & Kensler, C. J., 1966. Cancer Res. 26: 202–207.

    Google Scholar 

  53. Yesair, D. W., Rogers, W. I., Funkhouser, J. T. & Kensler, C. J., 1966. J. Lipid Res. 7: 492–500.

    Google Scholar 

  54. Marxer, A., 1967. Experientia 23: 173–174.

    Google Scholar 

  55. Mihich, E. & Gelzer, J., 1968. Cancer Res. 28: 553–558.

    Google Scholar 

  56. Mihich, E., 1975. In: Handbook of Experimental Pharmacology: Antineoplastic and Immunosuppressive Agents (Brodie, B. B. & Gillette, J. R., eds), vol. 38, part 2, pp. 766–788, Springer Verlag, Berlin.

  57. Dave, C., Ehrke, M. J. & Mihich, E., 1977. Chem. Biol. Interact. 16: 57–68.

    Google Scholar 

  58. Denny, W. A. & Cain, B. F., 1979. J. Med. Chem. 22: 1234–1239.

    Google Scholar 

  59. Regelson, W. & Holland, J. F., 1963. Cancer Chemother. Rep. 27: 15–26.

    Google Scholar 

  60. Knight, W. A., Livingston, R. B., Fabian, C. & Constanzi, J., 1979. Proc. Am. Assoc. Cancer Res. 20: 319.

    Google Scholar 

  61. Williams-Ashman, H. G. & Schenone, A., 1972. Biochem. Biophys. Res. Commun. 46: 288–295.

    Google Scholar 

  62. Corti, A., Dave, C., Williams-Ashman, H. G., Mihich, E. & Schenone, A., 1974. Biochem. J. 139: 351–357.

    Google Scholar 

  63. Janne, J., Poso, H. & Raina, A., 1978. Biochem. Biophys. Acta 473: 241–293.

    Google Scholar 

  64. Pine, M. J. & Di Paolo, J., 1966. Cancer Res. 26: 18–25.

    Google Scholar 

  65. Pleshkewych, A., Kramer, D. L., Kelly, E. & Porter, C. W., 1980. Cancer Res. 40: 4533–4540.

    Google Scholar 

  66. Atwell, G. J. & Cain, B. F., 1967. J. Med. Chem. 10: 706–713.

    Google Scholar 

  67. Denny, W. A., Atwell, G. J., Baguley, B. C. & Cain, B. F., 1979. J. Med. Chem. 22: 134–150.

    Google Scholar 

  68. Walls, L. P., 1963. Progr. Med. Chem. 3: 52–88.

    Google Scholar 

  69. Hansch, C., 1971. Chem. Rev. 71: 525–525

    Google Scholar 

  70. Atwell, G. J. & Cain, B. F., 1968. J. Med. Chem. 11: 295–300.

    Google Scholar 

  71. Atwell, G. J. & Cain, B. F., 1973. J. Med. Chem. 16:673–678.

    Google Scholar 

  72. Kensler, C. J., Palm, P. E., Day, H. M., Battista, S. P., Rogers, W. I. & Yesair, D. W., 1965. Cancer. Res. 25: 1622–1667.

    Google Scholar 

  73. Plowman, J. & Adamson, R. H., 1978. Pharmacology 17: 61–68.

    Google Scholar 

  74. Cain, B. F. & Atwell, G. J., 1976. J. Med. Chem. 19: 1417–1419.

    Google Scholar 

  75. Selsing, E., Wells, R. D., Alden, C. J. & Arnott, S., 1979. J. Biol. Chem. 254: 5417–5422.

    Google Scholar 

  76. Dattagupta, N., Hogan, M. & Crothers, D. M., 1978. Proc. Natl. Acad. Sci. U.S.A. 75: 4286–4290.

    Google Scholar 

  77. Gursky, G. V., Tumanyan, V. G., Zasedatelev, A. S., Zhuze, A. L., Grokhovsky, S. L. & Gottikh, B. P., 1976. Mol. Biol. Reports 2: 413–425.

    Google Scholar 

  78. Counsilman, A. C., Cain, B. F. & Baguley, B. C., 1974. Eur. J. Cancer 10: 75–81.

    Google Scholar 

  79. Counsilman, A. C., 1972. M. Sc Thesis, University of Auckland, New Zealand.

    Google Scholar 

  80. Robertson, I. G. C., 1978. Ph.D. Dissertation, University of Auckland, New Zealand.

    Google Scholar 

  81. Robertson, I. G. C., Denny, W. A. & Baguley, B. C., 1980. Eur. J. Cancer 16: 1133–1139.

    Article  Google Scholar 

  82. Anderson, W. A., Boivin, J., Monneret, C. & Pais, M., 1980. Mutation Res. 72: 341–346.

    Google Scholar 

  83. Bénard, J. & Riou, G. F., 1980. Biochemistry 19: 4197–4201.

    Google Scholar 

  84. Nagley, P., Mattick, J. S., Hall, R. M. & Linnane, A. W., 1975. Mol. Gen. Genet. 141: 291–304.

    Google Scholar 

  85. Burchenal, J. H., Coley, V., Purple, J. R., Bucholz, E., Lyman, M. S. & Kreis, W., 1963. Cancer Res. 23: 1364–1374.

    Google Scholar 

  86. Kensler, C., 1963. Cancer Res. 23: 1353–1363.

    Google Scholar 

  87. Baguley, B. C. & Nash, R., 1981. Eur. J. Cancer 17: 671–679.

    Google Scholar 

  88. Loewe, H. & Urbanietz, J., 1974. Arzneim. Forsch. 24: 1927–1933.

    Google Scholar 

  89. Comings, D. E., 1978. Ann. Rev. Genet. 12: 25–46.

    Google Scholar 

  90. Patterson, J. S. & Battersby, L. A., 1980. Cancer Treat. Rep. 64: 775–778.

    Google Scholar 

  91. Furr, B. J., Patterson, J. S., Richardson, D. N., Slater, S. R. & Wakeling, A. E., 1979. In: Pharmacological and Biochemical Properties of Drug Substances (Goldberg, M. E., ed), vol. 2, A.P.A., Washington.

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  1. Cancer Research Laboratory, University of Auckland Medical School, Private Bag, Auckland, New Zealand

    B. C. Baguley

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Baguley, B.C. Nonintercalative DNA-binding antitumour compounds. Mol Cell Biochem 43, 167–181 (1982). https://doi.org/10.1007/BF00223008

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