Photobehaviour and in vitro binding strategy of natural drug, chlorogenic acid with DNA: A case of groove binding

Abstract

Chlorogenic acid (CHA), a non-toxic natural drug exhibits a wide range of pharmacological potential including anti-diabetic and anti-carcinogenic activities. The molecular mechanism behind the interaction of CHA with DNA has not yet been addressed, while its pharmacological activities have been reported. The sensible DNA targeting protocol by phytochemicals like CHA not only offers an insight into the designing of more efficient drugs, but also leading the way towards the establishment of therapeutic agents for the regulation of gene expressions. This study unravelled the binding mode of CHA with calf thymus DNA (ct-DNA) through a series of spectroscopic, calorimetric, dye displacement and molecular docking analysis. The binding constants obtained from the fluorescence and the UV absorption experiments were consistently in the order of 103 Mol−1 with the renowned minor groove binders. The dye displacement studies using fluorophores conjugated ct-DNA systems confirmed the minor groove binding of CHA. The energetics of interactions explored from ITC revealed a spontaneous and enthalpy driven exothermic association. The CD and FTIR analysis provide specific evidences regarding the conformational alterations and the stability aspects of ct-DNA in the presence of CHA. The experimental data were further compared with supporting molecular docking analysis and hence our investigations confirmed that CHA binds in the minor groove of ct-DNA without causing significant structural alteration to the DNA. The information regarding CHA deduced from the current work disclosed better binding affinities and selectivity towards ct-DNA may be considered as a prime compound for the development of better drugs with therapeutic efficacy.