Search In this Thesis
   Search In this Thesis  
العنوان
DNA interaction studies of new transition metal complexes containing nitrogen donors /
المؤلف
Shabana, Ahmed Ahmed Zain Al-Abdeen Mohamed Ahmed.
هيئة الاعداد
باحث / احمد احمد زين العابدين محمد احمد شبانه
مشرف / سحر ابراهيم حامد مصطفي
مشرف / محسن مصطفي
مشرف / ايان بتلر
مشرف / برتنارد جون كلود
الموضوع
Chemistry, Inorganic.
تاريخ النشر
2015.
عدد الصفحات
xii, p. 188. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
كيمياء المواد
تاريخ الإجازة
1/1/2015
مكان الإجازة
جامعة المنصورة - كلية العلوم - قسم الكيمياء
الفهرس
Only 14 pages are availabe for public view

from 241

from 241

Abstract

Metal-based chemotherapeutic agents have gained considerable attention after the discovery of cisplatin, cis-[Pt(NH3)2Cl2], which is one of the best known small metal-containing drug molecules. It acts as anticancer agent for several human cancers, particularly, testicular and ovarian cancers. Generally, the side effects, especially nephrotoxicity, limit its widespread use in high doses. The need to develop new transition metal complexes with higher activity and lower nephrotoxicity has stimulated the synthesis of new complexes with promising non-toxic chelates. Since DNA replication is a key event for cell division, it is a critically important target in cancer chemotherapy. As DNA is the primary pharmacological target of many antitumor compounds, DNA-metal complex interactions have paramount importance in understanding the mechanism of tumour inhibition in the treatment of cancer. Circular dichroism spectroscopy (CD) is an optical technique that measures the difference in the absorption of left and right circularly polarized light. This technique has been widely employed in the studies of nucleic acids structures and to monitor the conformational polymorphism of DNA. DNA may undergo conformational changes to the B-form, A-form, Z-form, quadruplexes, triplexes and other structures as a result of the binding process to different compounds. CD has been used to obtain structural information about the global changes in DNA conformation induced by metal complexes. Most cytotoxic platinum drugs form strong covalent bonds with the DNA bases. However, a variety of platinum complexes act as DNA intercalators upon coordinating the appropriate ancillary ligands. There are also reports on palladium derivatives interacting with DNA in covalent and noncovalent ways. The main goals of this study is to develop new complexes with high efficacy against cancer cells. The choice of the human breast cancer (MDA-MB231) and human ovarian cancer (OVCAR-8) cell lines is due to their high incidence rate in the world. In addition, the choice of 2-aminobenzothiazole (Habt) and the pair of enantiomeric chiral, -1,2–bis-(1H-benzimidazol-2-yl)-1,2-ethanediol (-H2bie) and -1,2–bis-(1H-benzimidazol-2-yl)-1,2-ethanediol (-H2bie), is due to their low or non-cytotoxicity as well as the interest of many researchers in their anticancer activity. Moreover, the choice of metal ions plays an important role in the design of metal-based chemotherapeutic drugs. The biocompatible Zn(II) ion can be utilized to minimize the toxicity, as it is familiar with the biological environment of the human body. The second- and third-row transition metal ions, Pd(II), Pt(II), Ag(I) and Au(III), have low hydrolysis rates, which is also a recommended feature for the biological systems. The thesis consists of three main chapters, viz., Chapter 1 (Introduction), which presents an overview of the pertinent literature; Chapter 2 (Experimental) which describes the methods and measurements employed in this study as well as the methods of preparation of the complexes and the conditions employed for the biological applications; and Chapter 3 (Results and Discussion), which is dealing with the characterization of the complexes, the in vitro anticancer activity and the in vitro DNA studies, which were carried out by circular dichroism (CD) spectroscopy.