Abstract
The interaction of the anthracycline antitumor antibotics daunomycin and novatrone with the vitamin nicotinamide has been studied by one-and two-dimensional 1H NMR (500 MHz). Due to significant differences between the structures of the chromophores of interacting molecules, a two-site heteroassociation model has been developed, which implies the binding of one or several nicotinamide molecules to the chromophore of the antibiotic. The structural and thermodynamic parameters of the heteroassociation of nicotinamide with daunomycin and novatrone have been determined from the experimental concentration and temperature dependences of the 1H NMR chemical shifts of the interacting molecules. The most favorable structures of the 1:1 nicotinamide-daunomycin and nicotinamide-novatrone heterocomplexes have been found using the molecular mechanics method (X-PLOR software) and analysis of induced proton chemical shifts. The results demonstrate that two nicotinamide molecules cannot simultaneously bind on one side of the chromophore of the daunomycin or novatrone. The 1:1 heterocomplexes of the vitamin with the antibiotics are mainly stabilized by the stacking of aromatic chromophores.
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Abbreviations
- BAC:
-
biologically active compound
- NMD:
-
nicotinamide
- NOV:
-
novatrone
- DAU:
-
daunomycin
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Original Russian Text © A.O. Rozvadovskaya, V.P. Evstigneev, D.B. Davies, M.P. Evstigneev, 2006, published in Biofizika, 2006, Vol. 51, No. 2, pp. 214–224.
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Rozvadovskaya, A.O., Evstigneev, V.P., Davies, D.B. et al. Interaction between aromatic antibiotics and vitamins: 1H NMR study of heteroassociation of nicotinamide and anthracycline antitumor antibiotics. BIOPHYSICS 51, 176–185 (2006). https://doi.org/10.1134/S0006350906020047
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DOI: https://doi.org/10.1134/S0006350906020047