Interactions between DNA and benzo- and tetrahydrobenzofurocoumarins: thermodynamic and molecular modeling studies

The non-covalent interaction of a series of new water-soluble benzo- and te trahydrobenzofurocoumarins with salmon testes DNA has been studied using fl ow linear dichroism, circular dichroism, contact fluorescence energy transf er and ethidium bromide displacement assay. The new derivatives are charact erised by having an alkyl amino side chain protonated at physiological pH; this fact strongly enhances the solubility in aqueous media and the affinit y for the macromolecule. The results show significant difference in the aff inity and the mode of binding among the examined compounds depending on the nature of the fourth condensed ring and the position of the alkylamino sid e chain. Benzofurocoumarins derivatives bind DNA by undergoing intercalatio n inside the duplex macromolecule, whereas tetrahydrobenzofurocoumarins der ivatives show a substantial tilt relative to the base planes. Molecular mod eling studies have been performed to characterise in detail the intercalati on mechanism of these benzofurocoumarins to DNA. (C) 2000 Published by Else vier Science S.A. All rights reserved.