Synthesis Of 1,2-Dihydroquinoline Derivatives And Interaction With Biological Macromolecules

SA and DNA is an important part of organism which has the functions of transportation and maintain the stability of metabolism. In recent years, the interaction of small molecules with biological macromolecules caused the wide attention of researchers in the filed of chemistry, life science, clinical medicine and so on.Dihydrogen quinoline derivatives possess many bioactivities such as anti-inflammatory, antibacterial, antioxidant and anti-tumor, so they are widely used in the design of new drugs, but also can be used as a pesticide. The study found that the substituent of 1,2-dihydrogen quinoline has a better biological activity,such as 2,2-disubstitution dihydrogen quinolines HSA the function of inhibiting HIV-1 reverse transcriptase, in addition, 2,2,4-trisubstitution dihydrogen quinolines can be used as glucocorticoid receptor modulators, lipid peroxidation inhibitors, antioxidants, and inhibit the proliferation of proliferation cells by disrupting the redox balance without affecting the biological activities of normal cells. In this work, two kinds of modified 1,2-dihydrogen quinolines were disigned and synthesised. And their interaction with HSA and ctDNA, respectively, were explored by fluorescence spectrum, resonance light scattering spectrum, ultraviolet spectrum, CD spectrum and molecular docking. The specific contents are as follows:The first part: two new compounds 2-methyl-2,4-diethoxycarbonyl-6-trifluoromethoxy-1,2-dihydroquinoline(MDTDQ) and 2-methyl-2,4-diethoxycarbonyl-6,7-dichloro-1,2-dihydroquinoline(MDDDQ) were synthesised and characterized by 1H NMR, 13 C NMR, MS.The second part: The methods such as electrochemical impedance spectroscopy(EIS), resonance light scattering(RLS), ultraviolet absorption spectrum,fluorescence spectrum,circular dichroism spectrum,molecular simulation were used to study the mechanism of MDTDQ binding to serum albumin under simulated physiological conditions. The results of EIS and RLS showed that MDTDQ might bind to HSA via the formation a MDTDQ-HSA complex. The fluorescence of HSA was quenched by MDTDQ and the mechanism was proved to be static quenching procedure according to UV-vis absorbance spectroscopy and quenching rate constant which was calculated under three temperatures(298 K?304 K?310 K). Binding constants(Ka) and binding site number(n) and the binding distance(r) was calculated from corresponding equation. The major force between MDTDQ and HSA has been proved to be hydrogen bonding and van der Waals force according to the thermodynamic parameter. Effect of MDTDQ on the conformation of HSA has been investigated by means of synchronous fluorescence spectroscopy and CD specture. And the analysis of molecular docking showed that the binding site of MDTDQ and HSA was site I. In addition, the mechanism of interaction between MDTDQ and ctDNA was explored by fluorescence specture, CD specture, ultraviolet absorption spectrum and molecular docking simulation technology with acridine orange as fluorescent probe. The results demonstrated that the combination of MDTDQ and ctDNA was groove binding.The third part: Interaction of MDDDQ with biological macromolecules(HSA) was studied by the spectral methods. The study between MDDDQ and HSA revealed that MDDDQ might bind to HSA via to form a MDTDQ-HSA complex. The fluorescence of HSA was quenched by MDTDQ and the mechanism was proved to be static quenching procedure. Binding parameters(Ka?n?r) were obtained and the type of acting force between HSA and MDDDQ can be judged by the thermodynamic parameters. Moreover, conformational changes of HSA was explored by synchronous fluorescence and CD spectra.