Probing the Strength and Mechanism of Binding Between Amifampridine and Calf Thymus DNA.

In this work, we have investigated the strength and mechanism of amifampridine (3,4-Diaminopyridine/3,4-DAP) interaction with calf thymus DNA (ct-DNA). The existence and the strength of interaction are evaluated using circular dichroism (CD), UV-vis absorption, and differential pulse voltammogram studies. Results from UV-vis absorption technique indicate that amifampridine can significantly interact with DNA through a binding constant of Kb = 1.66 × 105 M-1 at 298 K. The mechanism of the interaction between amifampridine and DNA is also studied using ionic effect investigations, competitive fluorescence experiments, viscosity measurements, and molecular docking studies. The viscosity results indicate that amifampridine can bind to DNA via intercalation binding mode. Competitive fluorescence experiments using Acridine Orange (AO) and Hoechst 33258 (HO) probes also reveal that amifampridine binds to DNA via an intercalation mode of binding. Finally, the molecular docking studies also suggest that amifampridine tends to bind with the G-C rich region of DNA.

[1]  Adam Smith,et al.  Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug , 2020, The Annals of pharmacotherapy.

[2]  R. Mantegazza Amifampridine tablets for the treatment of Lambert-Eaton myasthenic syndrome , 2019, Expert review of clinical pharmacology.

[3]  S. Salehzadeh,et al.  Cytotoxicity and antioxidant activity of Kamolonol acetate from Ferula pseudalliacea, and studying its interactions with calf thymus DNA (ct-DNA) and human serum albumin (HSA) by spectroscopic and molecular docking techniques , 2019, Process Biochemistry.

[4]  O. Rajabi,et al.  Binding site identification of anticancer drug gefitinib to HSA and DNA in the presence of five different probes , 2019, Journal of biomolecular structure & dynamics.

[5]  S. Pawar,et al.  Spectroscopic and computational approaches to unravel the mode of binding between a isoflavone, biochanin-A and calf thymus DNA , 2019, Journal of biomolecular structure & dynamics.

[6]  M. Patel,et al.  Fluorescence and absorption studies of DNA-Pd(II) complex interaction: Synthesis, spectroanalytical investigations and biological activities. , 2019, Luminescence : the journal of biological and chemical luminescence.

[7]  S. Salehzadeh,et al.  In vitro cytotoxicity and DNA/HSA interaction study of triamterene using molecular modelling and multi-spectroscopic methods , 2018, Journal of biomolecular structure & dynamics.

[8]  S. Salehzadeh,et al.  Anticancer activity, calf thymus DNA and human serum albumin binding properties of Farnesiferol C from Ferula pseudalliacea , 2018, Journal of biomolecular structure & dynamics.

[9]  Shamsuzzaman,et al.  Unravelling the interaction of pirenzepine, a gastrointestinal disorder drug, with calf thymus DNA: An in vitro and molecular modelling study. , 2017, Archives of biochemistry and biophysics.

[10]  S. Salehzadeh,et al.  A multi-spectroscopic and molecular docking approach to investigate the interaction of antiviral drug oseltamivir with ct-DNA , 2017, Nucleosides, nucleotides & nucleic acids.

[11]  N. Shahabadi,et al.  Experimental and computational studies on the effects of valganciclovir as an antiviral drug on calf thymus DNA , 2017, Nucleosides, nucleotides & nucleic acids.

[12]  S. Salehzadeh,et al.  Binding Studies of Isoxsuprine Hydrochloride to Calf Thymus DNA Using Multispectroscopic and Molecular Docking Techniques , 2017, Journal of Fluorescence.

[13]  S. Tabassum,et al.  Synthesis and spectroscopic characterization of diorganotin(IV) complexes of N′-(4-hydroxypent-3-en-2-ylidene)isonicotinohydrazide: chemotherapeutic potential validation by in vitro interaction studies with DNA/HSA, DFT, molecular docking and cytotoxic activity , 2015 .

[14]  S. Rehman,et al.  Interaction of coumarin with calf thymus DNA: deciphering the mode of binding by in vitro studies. , 2015, International journal of biological macromolecules.

[15]  J. Iovanna,et al.  P8 deficiency increases cellular ROS and induces HO-1. , 2015, Archives of Biochemistry and Biophysics.

[16]  S. Rehman,et al.  Interaction of 6 Mercaptopurine with Calf Thymus DNA – Deciphering the Binding Mode and Photoinduced DNA Damage , 2014, PloS one.

[17]  P. Manisankar,et al.  Synthesis of mononuclear copper(II) complexes of acyclic Schiff's base ligands: spectral, structural, electrochemical, antibacterial, DNA binding and cleavage activity. , 2014, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[18]  S. Rehman,et al.  Naproxen intercalates with DNA and causes photocleavage through ROS generation , 2013, The FEBS journal.

[19]  N. Shahabadi,et al.  Study on the interaction of the drug mesalamine with calf thymus DNA using molecular docking and spectroscopic techniques. , 2013, Journal of photochemistry and photobiology. B, Biology.

[20]  N. Shahabadi,et al.  Study on the interaction of the antiviral drug, zidovudine with DNA using neutral red (NR) and methylene blue (MB) dyes , 2013 .

[21]  N. Shahabadi,et al.  Binding studies of the antidiabetic drug, metformin to calf thymus DNA using multispectroscopic methods. , 2012, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[22]  S. Kashanian,et al.  DNA binding, DNA cleavage and cytotoxicity studies of a new water soluble copper(II) complex: the effect of ligand shape on the mode of binding. , 2012, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[23]  Hanqi Zhang,et al.  Studies on the arctiin and its interaction with DNA by spectral methods , 2011 .

[24]  H. Tajmir-Riahi,et al.  Bundling and aggregation of DNA by cationic dendrimers. , 2011, Biomacromolecules.

[25]  B. Aggarwal,et al.  Models for prevention and treatment of cancer: problems vs promises. , 2009, Biochemical pharmacology.

[26]  A. Bonincontro,et al.  Dynamics of DNA adsorption on and release from SDS-DDAB cat-anionic vesicles: a multitechnique study. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[27]  Paul J Hergenrother,et al.  DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action. , 2007, Current opinion in biotechnology.

[28]  X. Bu,et al.  Two new Co(II) and Ni(II) complexes with 3-(2-Pyridyl)pyrazole-based ligand: synthesis, crystal structures, and bioactivities. , 2007, Chemical & pharmaceutical bulletin.

[29]  Ali Akbar Saboury,et al.  Stability and structural features of DNA intercalation with ethidium bromide, acridine orange and methylene blue , 2007 .

[30]  Wen Zhou,et al.  Determination of nucleic acids based on the fluorescence quenching of Hoechst 33258 at pH 4.5 , 2006 .

[31]  Remo Rohs,et al.  Molecular flexibility in ab initio drug docking to DNA: binding-site and binding-mode transitions in all-atom Monte Carlo simulations , 2005, Nucleic acids research.