Stacking and edge-to-edge associations of antitumoral ellipticine derivatives are controlled in solution by interactions involving their nitrogen sites
✍ Scribed by P. Sizun; C. Auclair; E. Lescot; C. Paoletti; B. Perly; S. Fermandjian
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 1988
- Tongue
- English
- Weight
- 596 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Synopsis
'H chemical shift dilution experiments on the cytotoxic drugs 2-methylellipticinium 1 and its methylated still active analogues 2,6-dimethylellipticini~m 2 and 1,2-dimethylellipticinium 3 indicate that the three chromophores autoassociate in dimers, trimers, and larger aggregates. The results suggest that the same chromophores are both stacked via transannular ?I interactions and associated edge to edge via interactions involving the nitrogen atoms such that layer structures similar to those observed in crystals could be formed at high concentration. Substitution with a methyl group on the N, position or the C , position near the N; , results in analogues displaying an association constant significantly reduced when compared to parent compound 1. This decrease is attributed to the loss or strength weakening of the forces involving nitrogen atoms rather than to the steric influence of the methyl substituents on the stacking of chromophores.
The results are further discussed in terms of the various modes of binding of the ellipticines to DNA.