DNA binding interaction studies of flavonoid complexes of Cu(II) and Fe(II) and determination of their chemotherapeutic potential

Abstract

The present study is based on molecular level investigation of DNA binding of three flavonoids (Fls), morin (mor), quercetin (quer) and primuletin (prim) and their metal (Cu (II) and Fe (III)) complexes through UV–Vis spectroscopy, fluorescence spectroscopy, thermal analysis and cyclic voltammetry (CV). The spectroscopic experiments were performed by titrating compounds with DNA and the results were in good agreement with those obtained from titration of DNA by the compounds. The Fe-mor, Cu-quer, Fe-quer and prim which exhibited hypsochromic/hyperchromic shifts in UV–Vis spectra, showed negligible effects over florescent spectra of NR-DNA (intercalating Neil red dye–DNA complex), intact Tm (thermal melting temperature) of DNA and the shift of peak potential (Ep) towards less positive value were designated to exhibit electrostatic mode of binding with dsDNA having binding constant, Kb ≈ 102 M−1. The mor, Cu-mor, Cu-prim and Fe-prim showed intercalating mode of interaction with dsDNA which was recognized from hypochromic/bathochromic shifts in the spectra, Ep shifts towards higher potential in CV, significant decay in fluorescence intensity, distinct shift in Tm of DNA and binding constant (Kb) of the order of 104 M−1. The mor exhibited mixed binding mode (intercalation and groove binding) at different concentrations. The quer displayed increase in peak current and hyperchromism thus depicted groove binding into dsDNA (Kb ≈ 103 M−1). The binding modes were found to be correlated with the apoptotic activity of the Fls and M-Fls (flavonoids and metal-flavonoids) assayed against human breast cancer cell lines (MCF-7) and human uterine cervical cancer cell lines (HeLa). The correlation is interpreted in terms of, the intercalation mode as cytostatic activity and the groove binding with no apoptosis. However, electrostatic binding of (M-)Fls to dsDNA did not produce significant anti-proliferation activity against Hela cell lines with exception of Fe-mor (cytostatic activity) and Cu-quer (cytotoxicity) against MCF-7 cell line.