title: Deciphering the interactions between chlorambucil and calf thymus DNA: a multi-spectroscopic and molecular docking study.
abstract: Non-covalent interactions of chlorambucil with calf thymus DNA was investigated using multi-spectroscopic techniques and molecular docking study. Binding constant calculated was found to be 1.54×10(4)M(-1) at 290K, significantly lower than various known intercalators. Quenching process was found to be static as evident by biomolecular quenching constant. Thermodynamic parameters revealed the involvement of hydrophobic interactions and hydrogen bonds in the binding. Chlorambucil was found to interact via external binding mode and follow groove binding as it replaces Hoechst (a typical groove binder) from the groove of DNA but does not replace intercalating dyes including ethidium bromide and acridine orange from the DNA helix. These results were further supported by KI quenching experiments, DNA melting studies, CD spectroscopy and molecular docking.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
authors.forename: Sayeed Ur
authors.initials: SU
authors.lastname: Rehman
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
authors.forename: Tarique
authors.initials: T
authors.lastname: Sarwar
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
authors.forename: Hassan Mubarak
authors.initials: HM
authors.lastname: Ishqi
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
authors.forename: Mohammed Amir
authors.initials: MA
authors.lastname: Husain
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
authors.forename: Ziaul
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India. Electronic address: tabish.bcmlab@gmail.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tabish
mesh_terms: D000165:Acridine Orange / Q000737:chemistry; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D006690:Bisbenzimidazole / Q000737:chemistry; D002417:Cattle; D002699:Chlorambucil / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004996:Ethidium / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium; D000165:Acridine Orange; D006690:Bisbenzimidazole
keywords: Calf thymus DNA; Chlorambucil; Groove binding; Molecular docking; Non-covalent interactions