Exploring The Binding Affinity Between Several Camptothecins And DNA/Protein

With the continuous development of medical level and the development of anti-tumor drugs,although the number of patients with malignant tumors increases year by year,the mortality rate of tumors decreases all the time.Camptothecin is one of an important antitumor drug,it is a natural quinoline alkaloid which showing a broad spectrum of antitumor activity.Its unique mechanism of action as topoisomerase I(Top I)inhibitor has been attracting great attention.The poor water solubility of camptothecin and the instability of E-ring in vivo seriously limit its clinical application,so a large number of camptothecin derivatives have been synthesized which modified structures for solubility and stability,three of which(topotecan,irinotecan,and belotecan)have been used clinically,and some are in preclinical studies.Protein is the basic material of living body,and also the direct expression of genetic traits,which participates in many important life processes,nucleic acid is the carrier of genetic material and life information of living body,which is very important for the growth,development,functional expression and reproduction of living body.Proteins and nucleic acids are often selected as in vitro biological models to study the pharmacological effects and biological activities of drug molecules.Therefore,the study of the interaction between camptothecin drugs and proteins and DNA is of great significance to elucidate and reveal the pharmacodynamics and metabolic processes of camptothecin drugs.At the same time,it provides important reference information for the design and development of a new generation of camptothecin drugs.In this paper,several camptothecin drugs with different structures were selected to interact with proteins and DNA by using modern spectroscopy method,biological electrochemical method and molecular docking technology analyses and studies the relationship between structural differences and affinity,we aim to use different research methods,study the interaction between camptothecin drugs and protein/DNA from different angles.This paper is divided into five chapters,the specific research contents are as follows:Chapter one: The structure,function,development history and research status of camptothecin are introduced,and the biomolecular models(serum albumin and DNA)are also introduced.Some common methods for studying interaction are summarized.The topic selection basis and research characteristics of this topic are also cleared.Chapter two: Uv-vis absorption spectroscopy,fluorescence spectroscopy,biological electrochemical method and molecular docking analysis were used to study the interaction between ct DNA and camptothecin and hydroxycamptothecin with acridine orange as the fluorescence probe.The action mechanism,binding mode and main force types were determined;at the same time,the relationship between different side chain groups and affinity was investigated.In addition,the effects of ionic strength,chemical denatured agent,acidity,thermal denaturation and heavy metal ions on the interaction between camptothecin drugs and ct DNA were investigated.Chapter three: The interaction of camptothecin,hydroxycamptothecin and vinpocetine with human serum albumin(HSA)was explored by Uv-vis absorption spectroscop,fluorescence spectrometry,circular dichroism,biological electrochemical method and molecular docking technology.The relationship between affinity and the difference of side chain groups and the molecular structure of the three drugs were studied,the quenching mechanism of the reaction system was investigated by Uv-vis and steady-state fluorescence experiments,and the quenching constants and binding constants were calculated;at the same time,the key information of the action site and the combination were simulated by means of molecular docking technology;Cyclic voltammetry and ac impedance experiments were applied to study the electrochemical behavior of the reaction system;The effects of three drugs on the molecular conformation of HSA were investigated by three-dimensional fluorescence and circular dichroism spectroscopy.Chapter four: The interaction of camptothecin,hydroxycamptothecin and vinpocetine with bovine serum albumin(BSA)was explored by Uv-vis absorption spectroscop,fluorescence spectrometry,circular dichroism,biological electrochemical method and molecular docking technology.The relationship between affinity and the difference of side chain groups and the molecular structure of the three drugs werestudied,the quenching mechanism of the reaction system was investigated by Uv-vis and steady-state fluorescence experiments,and the quenching constants and binding constants were calculated;at the same time,the key information of the action site and the combination were simulated by means of molecular docking technology;Cyclic voltammetry and ac impedance experiments were applied to study the electrochemical behavior of the reaction system;the effects of three drugs on the molecular conformation of BSA were investigated by synchronous fluorescence,three-dimensional fluorescence and circular dichroism spectroscopy;additional,the effect of heavy metal ions on the interaction between camptothecins and BSA was investigated.Chapter five: Summarize the whole paper;The interaction between camptothecin and biomolecules was prospected.