Investigating The Interaction Of Several Horizontal Drugs And Protein/DNA

Horizontal drugs are an important class of selective calcium channel blockers and a majority of horizontal drugs have physiological activity,which become a research hotspots in drug application.So far,this drug has been widely used in clinic.Horizontal drugs can not only reduce blood pressure by regulating calcium channels,but also have antiviral,antimicrobial and anti-inflammatory effects.In addition,horizontal drugs and their derivatives have wide practice prospects in cancer and other fields.Proteins and DNA are often selected as important in vitro biological models.This is because they are important undertakers of life activities and play an vital function in organisms.Therefore,exploring the interaction between horizontal drugs and biomacromolecules at the molecular level provides important reference value and research significance for understanding the mechanism of horizontal drugs in vivo.In addition,it provide a better idea for the screening and design of novel drugs.In this paper,horizontal drugs with different structures and biomacromolecules(proteins and DNA)are selected as the research objects,and non-spectral methods such as spectroscopy,electrochemistry and molecular simulation are used as research methods.The aim of this study is to study the affinity between small molecules and biomacromolecules of horizontal drugs under simulated physiological conditions by various methods and angles.This paper is divided into five chapters,the detail substances are as follows:Chapter 1: The classification,physiological activity and research progress of horizontal drugs are reviewed,and the common biomacromolecular models(proteins and DNA)are introduced.The research methods of drug small molecule and biomacromolecule were summarized.This paper briefly summarizes the basis,research characteristics of the topic in briefly.Chapter 2: The interaction of two horizontal drugs(nitrendipine and nicardipine hydrochloride)with human serum albumin(HSA)was explored by five methods:UV-Vis spectroscopy,fluorescence spectroscopy,infrared spectroscopy,electrochemistry and molecular simulation.The quenching mechanism of the system was debated with aid of fluorescence spectroscopy and UV-Vis spectroscopy.The quenching constants,binding constants and action sites of the reaction system were calculated.The effects of horizontal drugs on the secondary structure of HSA were investigated by synchronous fluorescence spectroscopy,three-dimensional fluorescence spectroscopy,UV-Vis spectroscopy and FT-IR.At the same time,The electrochemical behavior of the interaction between horizontal drugs and HSA was also studied by electrochemical method..The control mechanism of electrochemistry reaction was also investigated.the effects of the structure differences of horizontal drugs on the system were compared and analyzed.This chapter uses a variety of research methods to explore the interaction from multiple perspectives and verify the experimental results so that get more comprehensive and accurate information.Chapter 3: The interaction of four horizontal drugs(nifedipine,nisoldipine,nimodipine and nitrendipine)with bovine serum albumin(BSA)was explored by five methods: UV-Vis spectroscopy,fluorescence spectroscopy,infrared spectroscopy,electrochemical impedance spectroscopy and molecular simulation.The quenching mechanism of the system was debated with aid of fluorescence spectroscopy and UV-Vis spectroscopy.The quenching constants,binding constants and action sites of the reaction system were calculated.The effects of horizontal drugs on the secondary structure of BSA were discussed in detail.At the same time,the interaction between horizontal drugs and BSA was also studied by means of electrochemical impedance spectroscopic.The effects of different structures of horizontal drugs on the system were compared and analyzed.Based on the experimental results obtained by various methods,the structure-activity relationships of horizons were discussed and compared,which provided important reference for the design of new horizons.Chapter 4: The interaction of two horizontal drugs(nimodipine and nitrendipine)with ctDNA in the presence of molecular probes(acridine orange and hoechst)was explored by using five methods: UV-Vis spectroscopy,fluorescence spectroscopy,cyclic voltammetry,circular dichroism spectroscopy and molecular simulation.The impact of ionic strength,denaturant and acidity on the experimental system were investigated,which provided a reference for the best experimental conditions and designing fluorescence.At the same time,the interaction between horizontal drugs and ctDNA was also studied by means of cyclic voltammetry.the effects of structural differences of horizontal drugs on the system were compared.Chapter 5: Summarize the whole paper and give some suggestions on the affinity of horizontal drugs with biomacromolecules.