Structure-dependent of 3-fluorooxindole derivatives interacting with ctDNA: Binding effects and molecular docking approaches

• Published in: Bioorganic chemistry Vol. 121; p. 105698
• Main Authors: Huang, Ze-Yue, Wang, Zi-Heng, Niu, Ya, Deng, Guo-Xi, Bai, Ai-Min, Li, Xiao-Yun, Hu, Yan-Jun
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.04.2022; Elsevier
• Subjects: 3-fluorooxindoles; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; ctDNA; DNA - chemistry; Life Sciences & Biomedicine; Molecular docking; Molecular Docking Simulation; Multi-spectral; Nucleic Acid Conformation; Oxindoles; Physical Sciences; Science & Technology; Spectrometry, Fluorescence; Spectroscopy, Fourier Transform Infrared; Structure; Thermodynamics; 3-fluorooxindoles; Structure; Multi-spectral; ctDNA; Molecular docking; DAMAGE RESPONSE; CHEMISTRY; CALF THYMUS DNA
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2022.105698

[Display omitted] •Novel 3-fluorooxindole derivatives selected for research in biological applications.•Classical biomacromolecule DNA as a research model.•Combined multiple methods to investigate the binding mechanism between 3-fluorooxindoles and DNA.•The influence of substituents on interactions was analyzed by molecular planarity and space effects.•The structure-activity relationship between 3-fluorooxindoles and DNA were summarized. 3-Fluorooxindole has been shown to be a biologically active structural unit, novel derivative containing 3-fluorooxindole unit has been successfully constructed using 3-fluorooxindole as a substrate in previous work. Here, the interactions between novel 3-fluorooxindole derivatives and ctDNA were explored through molecular docking, multi-spectral and NMR methods, and the dependence of the binding mechanism on the structure was revealed by combined physical chemistry and organic chemistry. Firstly, molecular docking indicated that the planarity of the molecule enhances the binding strength to ctDNA. UV absorption result showed a weak binding effect. Fluorescence spectroscopy suggested the binding mechanism of 3-fluorooxindoles and ctDNA via groove binding. Moreover, the binding mechanism of 3-fluorooxindoles to ctDNA was further confirmed by 1H NMR spectroscopy, viscometry, and CD spectroscopy as groove binding. FT-IR spectroscopy reflected a more obvious disturbance of the phosphate group in the groove region of ctDNA. Electrochemistry was also used to probe the binding strength of 3-fluorooxindoles to ctDNA, and it showed a weak binding strength. From the above study, we concluded that 3-fluorooxindoles bind mainly in the groove region of ctDNA with weak binding strength. This study provides an idea for the activity screening aspect of 3-fluorooxindole derivatives from molecular planarity consideration and relevant information on biophysical and bioorganic aspects for drug development.