title: 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 (1)H 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: ΔH = 15.04 kJ mol(-1), ΔS = 105.54 J mol(-1) and ΔG = -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.
authors: Department of Medicinal Chemistry, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy - International Campus, Iran University of Medical Sciences, Tehran, Iran. Electronic address: fahmadi@kums.ac.ir.
authors: F
authors: F
authors: Ahmadi
authors: Department of Medicinal Chemistry, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors: S
authors: S
authors: Valadbeigi
authors: Department of Pharmacognosy, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: S E
authors: SE
authors: Sajjadi
authors: Department of Pharmacognosy, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors: Y
authors: Y
authors: Shokoohinia
authors: Department of Medicinal Chemistry, Faculty of Pharmacy - International Campus, Iran University of Medical Sciences, Tehran, Iran.
authors: H
authors: H
authors: Azizian
authors: Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors: G
authors: G
authors: Taheripak
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000737:chemistry; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004563:Electrochemistry; D004566:Electrodes; D007700:Kinetics; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010084:Oxidation-Reduction; D066244:Proton Magnetic Resonance Spectroscopy; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D003374:Coumarins; D004247:DNA; C427203:calf thymus DNA
keywords: DNA binding; Ferulago macrocarpa (Fenzl) Boiss; Grandivittin; Minor groove; Molecular docking