Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1979 Sep 11;7(1):217–230. doi: 10.1093/nar/7.1.217

Intercalative binding to DNA of antitumour drugs derived from 3-nitro-1,8-naphthalic acid.

M J Waring, A González, A Jiménez, D Vázquez
PMCID: PMC328007  PMID: 573892

Abstract

Two new antitumour drugs, imide derivatives of 3-nitro-1,8-naphthalic acid having different basic side chains linked to the imide nitrogen, have been shown to bind to double-helical DNA by intercalation. At ionic strength 0.01 mol/litre, pH 7, their intrinsic association constants are about 1.45 x 10(5) M-1 and each bound ligand molecule occludes about 3.4 nucleotides of the DNA lattice. They remove and reverse the supercoiling of closed circular duplex PM2 DNA with apparent unwinding angles of 11-12 degrees per bound drug molecule, referred to an assumed unwinding angle of 26 degrees for ethidium. They increase the viscosity of sonicated rod-like DNA fragments, each bound drug molecule producing a calculated increment in length of 2.2 - 2.5 A. No important differences between the DNA-binding characteristics of the two drugs were detected, though one appears marginally more active than the other in certain biological tests.

Full text

PDF
219

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balcarová Z., Kleinwächter V., Koudelka J. Interaction of phenosafranine with nucleic acids and model polyphosphates. II. Characterisation of phenosafranine binding to DNA. Biophys Chem. 1978 Mar;8(1):27–40. doi: 10.1016/0301-4622(78)85020-0. [DOI] [PubMed] [Google Scholar]
  2. COHEN S. N., YIELDING K. L. SPECTROPHOTOMETRIC STUDIES OF THE INTERACTION OF CHLOROQUINE WITH DEOXYRIBONUCLEIC ACID. J Biol Chem. 1965 Jul;240:3123–3131. [PubMed] [Google Scholar]
  3. Chandra P., Woltersdorf M. Influence of tilorone and cogeners on the secondary structure and template activity of DNA. FEBS Lett. 1974 Apr 15;41(1):169–173. doi: 10.1016/0014-5793(74)80980-4. [DOI] [PubMed] [Google Scholar]
  4. Cohen G., Eisenberg H. Conformation studies on the sodium and cesium salts of calf thymus deoxyribonucleic acid (DNA). Biopolymers. 1966 Apr-May;4(4):429–440. doi: 10.1002/bip.1966.360040404. [DOI] [PubMed] [Google Scholar]
  5. Crothers D. M. Calculation of binding isotherms for heterogenous polymers. Biopolymers. 1968 Apr;6(4):575–584. doi: 10.1002/bip.1968.360060411. [DOI] [PubMed] [Google Scholar]
  6. Espejo R. T., Canelo E. S., Sinsheimer R. L. DNA of bacteriophage PM2: a closed circular double-stranded molecule. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1164–1168. doi: 10.1073/pnas.63.4.1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Estensen R. D., Krey A. K., Hahn F. E. Studies on a deoxyribonucleic acid-quinine complex. Mol Pharmacol. 1969 Sep;5(5):532–541. [PubMed] [Google Scholar]
  8. Hogan M., Dattagupta N., Crothers D. M. Transient electric dichroism studies of the structure of the DNA complex with intercalated drugs. Biochemistry. 1979 Jan 23;18(2):280–288. doi: 10.1021/bi00569a007. [DOI] [PubMed] [Google Scholar]
  9. KUPCHAN S. M., DOSKOTCH R. W. TUMOR INHIBITORS. I. ARISTOLOCHIC ACID, THE ACTIVE PRINCIPLE OF ARISTOLOCHIA INDICA. J Med Pharm Chem. 1962 May;91:657–659. doi: 10.1021/jm01238a029. [DOI] [PubMed] [Google Scholar]
  10. Keller W. Determination of the number of superhelical turns in simian virus 40 DNA by gel electrophoresis. Proc Natl Acad Sci U S A. 1975 Dec;72(12):4876–4880. doi: 10.1073/pnas.72.12.4876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McGhee J. D., von Hippel P. H. Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J Mol Biol. 1974 Jun 25;86(2):469–489. doi: 10.1016/0022-2836(74)90031-x. [DOI] [PubMed] [Google Scholar]
  12. Müller W., Crothers D. M. Studies of the binding of actinomycin and related compounds to DNA. J Mol Biol. 1968 Jul 28;35(2):251–290. doi: 10.1016/s0022-2836(68)80024-5. [DOI] [PubMed] [Google Scholar]
  13. Reinert K. E. Adenosine-thymidine cluster-specific elongation and stiffening of DNA induced by the oligopeptide antibiotic netropsin. J Mol Biol. 1972 Dec 30;72(3):593–607. doi: 10.1016/0022-2836(72)90178-7. [DOI] [PubMed] [Google Scholar]
  14. Reinert K. E. DNA stiffening and elongation caused by the binding of ethidium bromide. Biochim Biophys Acta. 1973 Aug 24;319(2):135–139. doi: 10.1016/0005-2787(73)90004-x. [DOI] [PubMed] [Google Scholar]
  15. Wakelin L. P., Romanos M., Chen T. K., Glaubiger D., Canellakis E. S., Waring M. J. Structural limitations on the bifunctional intercalation of diacridines into DNA. Biochemistry. 1978 Nov 14;17(23):5057–5063. doi: 10.1021/bi00616a031. [DOI] [PubMed] [Google Scholar]
  16. Wakelin L. P., Waring M. J. The unwinding of circular deoxyribonucleic acid by phenanthridinium drugs: structure-activity relations for the intercalation reaction. Mol Pharmacol. 1974 May;10(3):544–561. [PubMed] [Google Scholar]
  17. Wakelin S. P., Waring M. J. The binding of echinomycin to deoxyribonucleic acid. Biochem J. 1976 Sep 1;157(3):721–740. doi: 10.1042/bj1570721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wang J. C. The degree of unwinding of the DNA helix by ethidium. I. Titration of twisted PM2 DNA molecules in alkaline cesium chloride density gradients. J Mol Biol. 1974 Nov 15;89(4):783–801. doi: 10.1016/0022-2836(74)90053-9. [DOI] [PubMed] [Google Scholar]
  19. Waring M. J. Complex formation between ethidium bromide and nucleic acids. J Mol Biol. 1965 Aug;13(1):269–282. doi: 10.1016/s0022-2836(65)80096-1. [DOI] [PubMed] [Google Scholar]
  20. Waring M. J. DNA-binding characteristics of acridinylmethanesulphonanilide drugs: comparison with antitumour properties. Eur J Cancer. 1976 Dec;12(12):995–1001. doi: 10.1016/0014-2964(76)90066-9. [DOI] [PubMed] [Google Scholar]
  21. Waring M. J., Wakelin L. P. Echinomycin: a bifunctional intercalating antibiotic. Nature. 1974 Dec 20;252(5485):653–657. doi: 10.1038/252653a0. [DOI] [PubMed] [Google Scholar]
  22. Waring M. Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs: evidence for molecular models involving intercalation. J Mol Biol. 1970 Dec 14;54(2):247–279. doi: 10.1016/0022-2836(70)90429-8. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES