Interaction of flavonoid topoisomerase I and II inhibitors with DNA oligomers

Abstract

The binding affinities of flavonoids, genistein and quercetin, to DNA oligomers have been established by means of studying by NMR the diffusion coefficients of these compounds with and without the presence of DNA. Genistein was found to bind very weakly, K_a = 1.54 × 10² M⁻¹, as compared to quercetin, K_a = 5.75 × 10³ M⁻¹ and luteolin, K_a = 2.17 × 10⁴ M⁻¹ (as reported in the literature). In the case of genistein a hydrogen bond between the NH^F,B cytidine protons of the edge base pair and a genistein hydroxyl is proposed, based on the shape of the DOSY spectrum. MP2 and DFT calculations of genistein show a 9 kcal mol⁻¹ excess energy of the planar conformation as compared with a twisted one. For this reason intercalation of the planar genistein into the base pairs is rather unlikely.