title: Racemic R,S-venlafaxine hydrochloride-DNA interaction: experimental and computational evidence.
abstract: The interaction of racemic R,S-venlafaxine hydrochloride (rac-VEN) drug with calf thymus deoxyribonucleic acid (ct-DNA) was studied using various physico-chemical techniques and molecular docking at simulated physiological conditions (pH=7.4). The fluorescence study shows that ct-DNA interacted with rac-VEN and quenched its intrinsic fluorescence in a static quenching process. These results are further supported by UV-Vis spectra. The binding constant of rac-VEN with ct-DNA (0.57 × 10(4)) obtained from the spectroscopic techniques, which is more in keeping with the groove binding with DNA. Furthermore, the competition experiment using Hoechst33258 indicated that rac-VEN may bind to ct-DNA by a minor groove binding mode. In addition, iodide quenching effect on the fluorescence of rac-VEN before and after the interaction with ct-DNA is another evidence to groove binding. The thermodynamic parameters are calculated by van't Hoff equation, which demonstrated that hydrogen bonds and van der Waals interactions played major roles in the binding reaction. Molecular simulation studies carried out by using the AutoDock4 and Spartan 10 programs. From the best docking map, we found that R and S-isomers fit in the A6T7T8/T19A18A17 region in minor groove of B-DNA. Finally, these results indicated that the docking of S-VEN-B-DNA is more stable than R-VEN-B-DNA.
authors: Inorganic Chemistry Department, Faculty of Chemistry, Razi University, Kermanshah, Iran; Medical Biology Research Center (MBRC) Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: NahidShahabadi@yahoo.com.
authors: Nahid
authors: N
authors: Shahabadi
authors: Inorganic Chemistry Department, Faculty of Chemistry, Razi University, Kermanshah, Iran.
authors: Saba
authors: S
authors: Hadidi
authors: Inorganic Chemistry Department, Faculty of Chemistry, Razi University, Kermanshah, Iran.
authors: Zeinab
authors: Z
authors: Ghasemian
authors: Organic Chemistry Department, Chemistry Faculty, Razi University, Kermanshah, Iran.
authors: Avat Arman
authors: AA
authors: Taherpour
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006690:Bisbenzimidazole / Q000737:chemistry; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D055664:Electrochemical Techniques; D004583:Electrons; D007454:Iodides / Q000737:chemistry; D007700:Kinetics; D008751:Methylene Blue / Q000737:chemistry; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D013237:Stereoisomerism; D013816:Thermodynamics; D000069470:Venlafaxine Hydrochloride / Q000737:chemistry / Q000378:metabolism*; D014783:Viscosity
chemical_list: D007454:Iodides; D000069470:Venlafaxine Hydrochloride; D004247:DNA; C427203:calf thymus DNA; D006690:Bisbenzimidazole; D008751:Methylene Blue
keywords: Groove binding; Molecular docking; Racemic R,S-venlafaxine hydrochloride drug; ct-DNA interaction