Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Dec;71(12):5078–5082. doi: 10.1073/pnas.71.12.5078

A New Antitumoral Agent: 9-Hydroxyellipticine. Possibility of a Rational Design of Anticancerous Drugs in the Series of DNA Intercalating Drugs

Jean-Bernard Le Pecq *, Nguyen-Dat-Xuong †, Charles Gosse *, Claude Paoletti *
PMCID: PMC434043  PMID: 4531039

Abstract

The designing of DNA intercalating drugs with high DNA affinity in the series of ellipticine has led to a new antitumoral agent, 9-hydroxyellipticine, which has a high DNA affinity, a high activity on L 1210 mice leukemia, and a lack of toxicity at therapeutic dose. The possible correlations among chemical structure, DNA reactivity, and pharmacological activity of DNA intercalating drugs are discussed.

Keywords: cancer chemotherapy, ethidium bromide, DNA unwinding, pyrido (4-3b) carbazole

Full text

PDF
5079

Selected References

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

  1. AUBIN G., CHENAILLE P., LAMONTHEZIE N., PAOLETTI C. [Extraction of desoxyribonucleic acid from different tissues using papain]. Biochim Biophys Acta. 1963 Jul 30;72:456–468. doi: 10.1016/0006-3002(63)90265-8. [DOI] [PubMed] [Google Scholar]
  2. Ames B. N., Durston W. E., Yamasaki E., Lee F. D. Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2281–2285. doi: 10.1073/pnas.70.8.2281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barthelemy-Clavey V., Maurizot J. C., Sicard P. J. Etude spectrophotométrique du complexe DNA-daunorubicine. Biochimie. 1973;55(8):859–868. doi: 10.1016/s0300-9084(73)80162-2. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Festy B., Poisson J., Paoletti C. A new DNA intercalating drug: Methoxy-9-ellipticine. FEBS Lett. 1971 Oct 1;17(2):321–323. doi: 10.1016/0014-5793(71)80176-x. [DOI] [PubMed] [Google Scholar]
  6. GELLERT M., SMITH C. E., NEVILLE D., FELSENFELD G. ACTINOMYCIN BINDING TO DNA: MECHANISM AND SPECIFICITY. J Mol Biol. 1965 Mar;11:445–457. doi: 10.1016/s0022-2836(65)80001-8. [DOI] [PubMed] [Google Scholar]
  7. Le Pecq J. B., Gosse C., Nguyen-Dat-Xuong, Paoletti C. Un nouveau composé anti-tumoral: l'hydroxy-9 ellipticine. Action sur la leucémie L 1210 de la souris. C R Acad Sci Hebd Seances Acad Sci D. 1973 Nov 19;277(20):2289–2291. [PubMed] [Google Scholar]
  8. LePecq J. B., Paoletti C. A fluorescent complex between ethidium bromide and nucleic acids. Physical-chemical characterization. J Mol Biol. 1967 Jul 14;27(1):87–106. doi: 10.1016/0022-2836(67)90353-1. [DOI] [PubMed] [Google Scholar]
  9. Li H. J., Crothers D. M. Relaxation studies of the proflavine-DNA complex: the kinetics of an intercalation reaction. J Mol Biol. 1969 Feb 14;39(3):461–477. doi: 10.1016/0022-2836(69)90138-7. [DOI] [PubMed] [Google Scholar]
  10. Mathé G., Hayat M., De Vassal F., Schwarzenberg L., Schneider M., Schlumberger J. R., Jasmin C., Rosenfeld C. Methoxy-9-ellipticine lactate. 3. Clinical screening: its action in acute myeloblastic leukaemia. Rev Eur Etud Clin Biol. 1970 May;15(5):541–545. [PubMed] [Google Scholar]
  12. Paoletti C., Cros S., Sorbara R., Gosse C., Tollon Y., Moisand C. Etudes sur la toxicité de la 9-hydroxyellipticine. C R Acad Sci Hebd Seances Acad Sci D. 1974 Mar 4;278(10):1437–1440. [PubMed] [Google Scholar]
  13. Rosenberg J. M., Seeman N. C., Kim J. J., Suddath F. L., Nicholas H. B., Rich A. Double helix at atomic resolution. Nature. 1973 May 18;243(5403):150–154. doi: 10.1038/243150a0. [DOI] [PubMed] [Google Scholar]
  14. Révet B. M., Schmir M., Vinograd J. Direct determination of the superhelix density of closed circular DNA by viscometric titration. Nat New Biol. 1971 Jan 6;229(1):10–13. doi: 10.1038/newbio229010a0. [DOI] [PubMed] [Google Scholar]
  15. SKIPPER H. E., SCHABEL F. M., Jr, WILCOX W. S. EXPERIMENTAL EVALUATION OF POTENTIAL ANTICANCER AGENTS. XIV. FURTHER STUDY OF CERTAIN BASIC CONCEPTS UNDERLYING CHEMOTHERAPY OF LEUKEMIA. Cancer Chemother Rep. 1965 Apr;45:5–28. [PubMed] [Google Scholar]
  16. Saucier J. M., Festy B., Le Pecq J. B. The change of the torsion of the DNA helix caused by intercalation. II. Measurement of the relative change of torsion induced by various intercalating drugs. Biochimie. 1971;53(9):973–980. doi: 10.1016/s0300-9084(71)80065-2. [DOI] [PubMed] [Google Scholar]
  17. Svoboda G. H., Poore G. A., Montfort M. L. Alkaloids of Ochrosia maculata Jacq. (Ochrosia borbonica Gmel.). Isolation of the alkaloids and study of the antitumor properties of 9-methoxyellipticine. J Pharm Sci. 1968 Oct;57(10):1720–1725. doi: 10.1002/jps.2600571019. [DOI] [PubMed] [Google Scholar]
  18. Wahl P., Paoletti J., Le Pecq J. B. Decay of fluorescence emission anisotropy of the ethidium bromide-DNA complex. Evidence for an internal motion in DNA. Proc Natl Acad Sci U S A. 1970 Feb;65(2):417–421. doi: 10.1073/pnas.65.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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 Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES