Characterization Of Interaction Of Anthracyclines Drugs With Deoxyribonucleic Acid

Deoxyribonucleic Acid (DNA) is one of the most basic genetic materials. It plays an important role in biological life activity. DNA carries the genetic information with organism, and is able to copy and transcription of the genetic information to guide the proteins and enzymes biosynthesis. The researches related to DNA are significant tasks of molecular biology and biochemistry. DNA is quite often the main cellular target with small molecules of biological importance. Scientific researchers pay more attention to the interaction of these molecules and DNA and this field has been a very active field. At present many clinical used anticancer drugs are based on DNA for the main targets. In tumor cells, the structure of DNA is destroyed after binding to drugs. The polymerase and nucleic acid synthesis is inhibited. The interaction between drugs and DNA is the foundation of understanding certain diseases pathogenic mechanism and drug cure mechanism. It has an important significance in clarifying the structure and function of DNA. Anthracyclines have a wide spectrum of biological activity and are very potent and often used anticancer drugs. Studies have demonstrated that anthracycline intercalate with DNA and partially uncoil the double-stranded helix. Various toxic effect such as cardiotoxicity makes the application of such medicines certain limits. In this paper, the interaction of anthracycline drugs with DNA were investigated, these anthracycline drugs included ADNR-3,ADNR,ADOX and AEPI. six chapters was contained in this dissertation.Chapter 1: The structures and functions of DNA; the bioactivities and functions of anthracyclines drugs; and the interaction research between DNA and drugs.Chapter 2: The binding of ADNR-3 to DNA was studied by spectroscopic method; The binding constant between ADNR-3 and DNA was 4.07×105 L·mol^-1,which indicated that there was a strong binding between ADNR-3 with DNA; The binding forces between them were hydrogen bonds force and Van der Waals' force; The absorption spectrum and fluorescent polorization indicated the major mode is intercalation binding between ADNR-3 and DNA.Chapter 3: The interaction of ADNR with DNA was first studied using UV spectra and fluorescence spectra; The quenching of the static type was attributed to the formations of ADNR-DNA complex; The experiment results also indicated that ADNR intercalated into the base pairs of DNA. The interaction force between ADNR and DNA were mainly hydrogen bonds force and Van der Waals' force.Chapter 4: Many methods were used to characterize the interaction of ADOX and DNA,the quenching constants and quenching mode were investigated according to Stern-Volmer equation, and double logarithmic equation was used to calculate the binding constants and binding sites; The absorption spectra and fluorescence polarization spectra indicated the major mode was intercalation binding between ADOX and DNA.Chapter 5: Fluorescence spectra were used to study the binding of AEPI and DNA; DNA could quenching the fluorescence of AEPI by forming a new compound; The mechanism of the quenching between AEPI and DNA was static; The binding constants indicated that binding force between AEPI and DNA was strong.Chapter 6: Summarizes and Prospects.