Grandivittin as a natural minor groove binder extracted from Ferulago macrocarpa to ct-DNA, experimental and in silico analysis

Abstract

Ferulago macrocarpa (Fenzl) Boiss., is an endemic medicinal herb of Iran. In this study a dihydrofuranocoumarin called grandivittin (GRA) was separate and purified from Ferulago macrocarpa (Fenzl) Boiss, and characterized by H-1 NMR and Mass spectroscopic methods. The electrochemical behavior of GRA was evaluated by cyclic voltammetry (CV). The interaction of GRA with calf thymus double strand deoxyribonucleic acid (ct-DNA), was evaluated by CV, differential pulse voltammetry (DPV), fluorescence, UV-Vis, FT-IR and molecular modeling methods. The thermodynamic parameters of GRA-DNA complex were measured and reported as: Delta H = 15.04 kJ mol(-1), Delta S = 105.54 J mol(-1) and Delta G = -15.62 kJ mol(-1). Docking simulation was performed to investigate the probable binding mode of GRA to various DNA, too. The polymerase extension study was performed using real-time PCR to confirm the inhibitory effect of GRA on polymerase extension activity as a mirror of binding to ct-DNA. However, all data showed that the grooves binding especially minor groove between GRA and ct-DNA is more predominant rather than other binding modes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.