Synthesis and study of an acridine substituted Tröger’s base: preferential binding of the (–)-isomer to B-DNA

Abstract

The acridine substituted Tröger’s base 4 was prepared, resolved and the (–)-(7R,17R) enantiomer was shown to bind preferentially to calf-thymus B-DNA.

References

1. B. Norden, P. Lincoln, B. Akerman and E. Tuite, in Metal Ions in Biological Systems, eds. A. Sigel and H. Sigel, Marcel Dekker, New York, 1996, vol. 33, ch. 7, pp. 205–252; C. M. Dupureur and J. K. Barton, Inorg. Chem., 1997, 36, 33 and references cited therein; S. Satyanarayana, J. C. Dabrowiak and J. B. Chaires, Biochemistry, 1993, 32, 2573; A. D. Baker, R. J. Morgan and T. C. Strekas, J. Am. Chem. Soc., 1991, 113, 1411.
2. For a review on Tröger's base, see: F. Vögtle, Fascinating Molecules in Organic Chemistry, J. Wiley, New York, 1992, pp. 237–249.
3. R. B. Silverman, The organic chemistry of drug design and drug action, Academic Press, San Diego, 1992, pp. 239–241.
4. Y. Coppel, Ce. Coulombeau, C. Coulombeau, J. Lhomme, M.-L. Dheu-Andries and P. Vatton, J. Biomol. Struct. Dyn., 1995, 12, 637.
5. A. Wardani and J. Lhomme, Tetrahedron Lett., 1993, 34, 6411.
6. A. Tatibouët, M. Demeunynck, H. Salez, R. Arnaud, J. Lhomme and C. Courseille, Bull. Soc. Chim. Fr., 1997, 134, 495.
7. H. Salez, A. Wardani, M. Demeunynck, A. Tatibouët and J. Lhomme, Tetrahedron Lett., 1995, 36, 1271; A. Tatibouët, M. Demeunynck and J. Lhomme, Synth. Commun., 1996, 26, 4375.
8. M. Demeunynck, C. Fontaine and J. Lhomme, Magn. Reson. Chem., 1998, in the press.
9. B. M. Wepster, Recl. Trav. Chim. Pays. Bas., 1953, 72, 661.
10. A. Greenberg, N. Molinaro and M. Lang, J. Org. Chem., 1984, 49, 1127.
11. N. Harada and K. Nakanishi, Circular Dichroic Spectroscopy, University Science Books, Mill Valley, California, 1983; See also: K. Nakanishi, N. Berova and R. W. Woody, Circular Dichroism, Principles and Applications, VCH, Weinhem, 1994.
12. This situation, which prevails in the exciton coupling of most C₂ systems, is supported in this specific case by examination of Dreiding models.
13. S. F. Mason, G. W. Vane, K. Schofield, R. J. Wells and J. S. Whitehust, J. Chem. Soc. (B), 1967, 553; S. H. Wilen, J. Z. Qi and P. G. Williard, J. Org. Chem., 1991, 56, 485.
14. The absorption wavelengths and the transition moments were calculated by means of a CNDO/S program parametrized to reproduce the properties of the molecules in solution: C. Andraud, T. Brotin, C. Garcia, F. Pellé, P. Goldner, B. Bigot and A. Collet, J. Am. Chem. Soc., 1994, 116, 2094; T. Brotin, C. Andraud, I. Ledoux, S. Brasselet, J. Zyss, M. Perrin, A. Thozet and A. Collet, Chem. Mater, 1996, 8, 890.
15. G. Lamm and G. Pack, Proc. Natl. Acad. Sci. U.S.A., 1990, 87, 9033.
16. S. S. Peacock, D. M. Walba, F. C. A. Gaeta, R. C. Helgeson and D. J. Cram, J. Am. Chem. Soc., 1980, 102, 2043.
17. Right-handed twist is also observed for other DNA intercalating drugs such as anthracyclines; for a review, see: J. W. Lown, Chem. Soc. Rev., 1993, 165.