title: Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative.
abstract: The present study embodies the detail DNA binding interaction of a potential bioactive quinoline appended chalcone derivative (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) with calf thymus DNA (ctDNA) and its consequences by UV-Vis absorption, steady state fluorescence spectroscopy, fluorescence anisotropy, circular dichromism, helix melting, agarose gel electrophoresis, molecular docking, Induced Fit Docking (IFD) and molecular dynamics (MD) simulation. The UV-Vis absorption and fluorescence study reveal that the molecule undergoes considerable interaction with the nucleic acid. The control KI quenching experiment shows the lesser accessibility of ADMQ molecule to the ionic quencher (I(-)) in presence of ctDNA as compared to the bulk aqueous phase. Insignificant change in helix melting temperature as well as in circular dichromism (CD) spectra points toward non-covalent groove binding interaction. The moderate rotational confinement of this chalcone derivative (anisotropy=0.106) trapped in the nucleic acid environment, the comparative displacement assay with well-known minor groove binder Hoechst 33258 and intercalator Ethidium Bromide establishes the minor groove binding interactions of the probe molecule. Molecular docking, IFD and MD simulation reveal that the DNA undergoes prominent morphological changes in terms of helix unwinding and bending to accommodate ADMQ in a crescent shape at an angle of 110° in a sequence specific manner. During interaction, ADMQ rigidifies and bends the sugar phosphate backbone of the nucleic acid and thereby shortens its overall length by 3.02Å. Agarose gel electrophoresis experiment with plasmid pBR 322 reveals that the groove binded ADMQ result in a concentration dependent cleavage of plasmid DNA into its supercoiled and nicked circular form. The consolidated spectroscopic research described herein provides quantitative insight into the interaction of a heterocyclic chalcone derivative with relevant target nucleic acid, which may be useful for the future research on chalcone based therapeutic agents.
authors.affiliation: Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India.
authors.forename: Himank
authors.initials: H
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai 600003, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Devaraji
authors.affiliation: Department of Chemistry, BITS-Pilani, K.K. Birla Goa Campus, Zuarinagar, Goa 403726, India.
authors.forename: Rangaraj
authors.initials: R
authors.lastname: Prasath
authors.affiliation: Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India.
authors.forename: Manojkumar
authors.initials: M
authors.lastname: Jadhao
authors.affiliation: Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India.
authors.forename: Ritika
authors.initials: R
authors.lastname: Joshi
authors.affiliation: Department of Chemistry, BITS-Pilani, K.K. Birla Goa Campus, Zuarinagar, Goa 403726, India.
authors.forename: Purushothaman
authors.initials: P
authors.lastname: Bhavana
authors.affiliation: Department of Chemistry, Visvesvaraya National Institute of Technology, Nagpur, Maharashtra 440010, India. Electronic address: skghosh@chm.vnit.ac.in.
authors.forename: Sujit Kumar
authors.initials: SK
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry* / Q000378:metabolism*; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D053837:DNA Cleavage; D005454:Fluorescence Polarization; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: C000597864:3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one; D000873:Anthracenes; D011804:Quinolines; D004247:DNA; C427203:calf thymus DNA
keywords: ADMQ; Anisotropy; Circular dichromism; Fluorescence quenching; Groove binding; Helix melting