Research On Biological Activities And Structure-activity Relationship Of Flavonoids

Flavonoids, a large group of plant metabolites(polyphenolic molecules) found commonly in fruits, vegetables, wine, and tea are known to colossal biological effects,such as antiviral, antioxidative, antibacterial and antiallergy activities due to their diversity in structure. The study on structure-activity relationship about biological activities could helpful for the development of their pharmacological effects.Molecular targets of drug mostly associated with proteins and DNA. The absorption and distribution of drug is influenced by protein, a carrier for therapeutic and diagnostic agents. At the same time, DNA is important in controlling the heredity of life and act as a drug target. The research about the interaction between drugs and biological macromolecules helps to expounding the mechanism of drugs at molecular level.So far, the research about structure-activity relationship is normally based on the animal experiment and clinical research etc. From the microscopic to macroscopic point of view, comparative analysis the effects of the differences in structure(the number and position of hydroxyl groups, the existed of double bond or not, the type of functional groups and so on) on the interaction between different flavonoids and macromolecules, combined with the measurement of antioxidant and anti-bacterial activity, could explain the biological effect and structure-activity relationship of flavonoids comprehensively, which may not only improve our understand on the mechanism behind versatile bioactivities of flavonoids but also provide a theoretical basis for subsequent design and development.The dissertation is separated in to five chapters and the main contents are as follow:Chapter one: In this chapter, the classification, biological activity, research hotspot, research situation of structure-activity relationship of flavonoids have been summarized. In addition, the research methods about the antioxidant activity measurement and the interaction between small molecules and biological macromolecules have been reviewed detailed. With the establishment of subject theory, the feasibility and importance of the study about biological activities and structure-activity relationship based on interaction have been explained and the main innovative points have been carried out.Chapter two: Fluorescence spectrometry, circular dichroism spectrometry incombination with molecular simulation have been employed for the study on biological activities and structure-activity relationship between three kinds of flavone,namely Baicalein, Wogonin and Chrysin. The quenching degree, quenching mechanism, binding site and the main binding force between different flavone and BSA have been analyzed comparatively. In addition, calculated quenching constants,binding constants, thermodynamic parameters and their effect to protein,s structure have been compared too. The biological activity and structure-activity relationship have been got preliminary which could provide basic parameters for the research on subsequent flavone.Chapter three: Fluorescence spectrometry, electrochemical method and molecular simulation have been employed for the study on biological activities and structure-activity relationship between different flavonoids, namely flavone(Baicalein,Wogonin and Chrysin), flavonol(Quercetin) and dihydroflavone(Naringenin). The quenching degree, quenching mechanism, binding site, the main binding force, the effect of chemical denaturant(urea and guanidine) and conformation influence between different flavonoids and HSA have been analyzed comparatively.Furthermore, the effect of structure(skeleton structure, functional group, the double bond) to the interaction results has been summaried, which may provide the reference information for the design and development of flavonoids targeted to serum albumin.Chapter four: Fluorescence spectrometry, electrochemical method and molecular simulation have been employed for the study on biological activities and structure-activity relationship between different flavonoids, namely flavone(Baicalein,Wogonin and Chrysin), flavonol(Quercetin) and dihydroflavone(Naringenin) based on their interaction with DNA. Different fluorescent probes have been introduced for the interaction mode investigation of different flavonoids, and their effect to different DNA-probes has been compared. The quenching degree, quenching mechanism,binding mode and the effect of different conditions(temperature, chemical denaturant,pH values, ion strength, supermolecule) have been analyzed comparatively. In addition, the biological activity and structure-activity relationship between different flavonoids and DNA have been got which may provide theoretical basis for the design and development of flavonoids targeted to DNA.Chapter five: In this chapter, electrochemical methods, UV absorption spectrometry and microcalorimetry have been introduced for the measurement of electrochemical activity, antioxidant and antibacterial activity. The structure-activityrelationship and biological activities have been concluded consistent with clinical results which supported that the feasibility of related methods involved. The conclusion of this chapter could provide theoretical basis and reference for the design and development of subsequent antioxidant and antibacterial activity flavonoids.Chapter six: We summarized the conclusions systematically, and the work subsequent has been discussed. This chapter is expected to provide a reference for the structure-activity relationship research of flavonoids.