Binding site identification of anticancer drug gefitinib to HSA and DNA in the presence of five different probes. Issue 4 (4th March 2019)

• Record Type: Journal Article
• Authors: Tanzadehpanah, Hamid; Mahaki, Hanie; Moghadam, Neda Hosseinpour; Salehzadeh, Sadegh; Rajabi, Omid; Najafi, Rezvan; Amini, Razieh; Saidijam, Massoud
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 37:Issue 4(2019)
• Page Start: 823
• Page End: 836
• Publication Date: 2019-03-04
• Subjects: gefitinib -- human serum albumin -- calf thymus DNA -- fluorescence spectroscopy -- zeta potential -- molecular modeling; AO: Acridine Orange -- ATP: Adenosine TriPhosphate -- BSA: Bovine Serum Albumin -- ctDNA: calf thymus DNA -- DMSO: Dimethyl Sulfoxide -- EB: Ethidium Bromide -- FDA: Food and Drug Administration -- FRET: Fluorescence Resonance Energy Transfer -- GEF: Gefitinib -- HO: Hoechst -- HSA: Human Serum Albumin -- IBU: Ibuprofen -- MB: Methylene Blue -- WAR: Warfarin -- ΔG: Gibbs free energy -- ΔH: Enthalpy changes -- ΔS: Entropy changes; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2018.1441073
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract : This study was carried out to evaluate the binding interaction of gefitinib (GEF) with human serum albumin (HSA) and calf thymus DNA (ct-DNA) using fluorescence, UV–Visible, zeta potential measurements and molecular docking methods in order to understand its pharmacokinetic mechanism. By increasing the temperature, a steady decrease in Stern–Volmer quenching constants was observed for HSA binding properties; this indicates a static type of fluorescence quenching. Negative values were calculated for Gibbs free energy (Δ G ), enthalpy (Δ H ), and entropy (Δ S ) changes, indicating that the reaction is spontaneous and enthalpy-driven. Probe competitive experimental results showed that GEF contains the same binding site as warfarin and are consistent with modeling results. The zeta potential of the HSA increased with increasing GEF, which represents the presence of electrostatic interactions in the system. DNA binding properties were investigated in the presence of three probes. The experimental results showed that by increasing GEF to DNA-AO (acridine-orange) and DNA-MB (methylene-blue) system, the fluorescence intensity and absorbance spectra had no considerable change. Furthermore, with the addition of GEF to DNA, the zeta potential decreased gradually, indicating that the hydrophobic interaction between the GEF and the bases of DNA is the major factor. Thus, GEF can bind to DNA via a groove binding mode. It was also found that GEF entered into the minor groove in the A–T rich region of DNA fragment and bind via van der-Waals forces and three H-bond with double strands of DNA. This is in good agreement with experimental results.