Interactions of therapeutically active plant flavonols with biological targets : Insights from fluorescence spectroscopic studies

Plant flavonols have attracted much recent attention in view of their novel therapeutic properties (effective against various free radical mediated and other diseases) which make them promising alternatives to conventional therapeutic drugs. However, till date, not much is known, regarding their mode of interactions and binding affinities with relevant biological targets. This article presents perspectives highlighting the usefulness of the exquisitely sensitive 'two color' fluorescence behavior of flavonols (which arise due to highly efficient photoinduced excited state intramolecular proton transfer (ESIPT) reactions) for exploring their interactions, at the molecular level, with biomembranes and proteins, which are the principal biological targets of such drug molecules. In this context, we made exploratory studies on the interactions of some representative therapeutically important flavonols with model and natural membranes (composed of phosphatidylcholine liposomes and red blood cell ghost membranes respectively) and serum albumin proteins. Since the ESIPT process is highly sensitive to external hydrogen bonding perturbation effects, the relative contribution between the two colors is strongly modulated by the local environment of the fluorophore, with dramatic changes in the emission yield, energy, anisotropy (r), lifetime (x) and related parameters of both ESIPT tautomer and normal fluorescence bands. This provides multiparametric fluorescence probing opportunities, revealing salient details about the nature and location or binding sites as well as quantitative estimates or partition coefficients/binding constants. This promising new approach may be expected to open up new avenues for the 'screening' of the most appropriate flavonoid derivatives, from among numerous structural variants found in nature, as well as the design of relevant synthetic derivatives with improved features.