الفهرس 
Chapter 1: IntroductionOnly 14 pages are availabe for public view
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Abstract
Thiosemicarbazones and their metal complexes have attracted considerable attention due to their great biological activities. The usage of several thiosemicarbazone derivatives in drug synthesis has resulted in extensive research on the chemistry and metabolism of these drugs.
The current thesis consists of three main chapters:
Chapter 1: Introduction
This chapter gives a literature survey about the definition of thiosemicarbazone, oxime compounds and their importance as well as their metal complexes especially those of biological activity. Also, the definition of cancer and the mechanism of Ehrlich Ascites carcinoma and solid tumor in mices are presented. It has been concentrated on the analytical and biological applications of thiosemicarbazones and their metal complexes
Chapter 2: materials and methods
This chapter describes the method of preparation of the ligand and the methods used to prepare the metal complexes of this ligand with metal salts of iron(III), cobalt (II), nickel (II), and copper(II). The ligand (H2L) was synthesized by mixing equimolar quantities of N(4)-antipyrinylthiosemicarbazide ,and syn-methyl anti-acetylmonoxime in anhydrous EtOH and then the mixture was heated (80oC) under reflux for 2h. Two drops of sulfuric acid (H2SO4) were added to the mixture in order to accelerate the reaction rate. The metal complexes of the ligand with Fe (III), Co(II), Ni(II) and Cu(II) ions were synthesized by mixing 30cm3 of a hot ethanolic solution of the metal salts: FeCl3.6H2O, CoCl2.6H2O, Co(OAc)2.4H2O, Co(NO3)2.6H2O, NiCl2.6H2O, Ni(OAc)2.4H2O, Ni(NO3)2.6H2O, CuCl2.2H2O, CuBr2, Cu(OAc)2.H2O and Cu(NO3)2.3H2O, with the appropriate amount of hot (75oC) ethanolic solution of the ligand
This chapter also describes the different techniques and instruments that were utilized for elucidation of structure of ligand and its metal complexes as elemental analyses, spectral techniques (FTIR, UV–Vis, 1H NMR, EPR and mass
spectra), magnetic susceptibility, molar conductivity and thermogravimetric measurements. Finally, the techniqes and istruments used for evaluation of biological activity of the prepared ligand and some of its metal complexes against solid tumor to establish their potential as anticancer agents were also descriped .
Mice were S.C. injected with EAC to induce solid tumors then divided into different groups for treatment with the prepared ligand and its different metal complexes for 14 consecutive days. At the end of experiments, blood was collected and serum samples were obtained by centrifugation at 2000 rpm for 10 min. and were kept at –20oC until assayed. Livers and solid tumors were removed and cut into pieces in individually separated, before fixation in paraffin blocks for immunohistochemical assays. One part was stored in 10% neutral buffered formalin solution for histopathological examination and the second part was kept frozen at –80 oC for further studies.
Chapter 3: Results and Discussion
This chapter includes the results of characterization of ligand and its metal complexes, as well as the results of the evaluation of their biological activities against EAC cells induced in mice. Also, the scientific discussion of the obtained results in the light of the published data was presented.
I- characterization of the prepared ligand and its metal complexes:-
In this section, the prepared ligand and its metal complexes were characterized by different standardized techniques to identity the prepared compounds. These techniques are 1H NMR, FTIR, UV-Vis, EPR, magnetic susceptibility, mass spectra, thermogravimetric (TGA), and molar conductivity measurements.
The ligand in these complexes behaves as a monobasic tridentate ligand coordinated through the azomethine nitrogen, oximino nitrogen and the thiol sulfur atoms.
The FT-IR spectra of metal complexes [Fe2(HL)2Cl4]·H2O (complex 1), [Co2(HL)2](NO3)2.H2O (complex 4) and [Ni2(HL)2](NO3)2·H2O (complex 7)
proved that these complexes are bi-nuclear. This is also evidenced by the mass spectra of complexes and the values of abnormal magnetic moment. The new FT-IR spectral bands observed in the spectra of complexes [Co(HL) (OAC)].H2O (3), [Ni(HL)(OAC)].H2O (6) and [Cu(HL)(OAC)].2H2O (10) indicating that the OAc- coordinated to the metal ion as a monodentate ligand. The infrared spectrum of complex [Cu(HL)(NO3)] (11) showed two bands characteristic to a monodentate nitrato ligand.
Electronic spectral bands of the ligand and its the complexes in both solution and solid state as well as magnetic moment values measured at room temperature, were discussed . The results of both electronic spectra and magnetic measurements indicated that : iron(III) complex displayed octahedral stereochemistry, cobalt(II) complexes 2, 3 and 4 exhibit tetrahedral arrangement around the Co(II) ion, nickel(II) complexes 5 and 6 are diamgnetic indicating a square planar steriochemisry , whereas, nickel(II) complex 7 displays a tetrahedral geometry. The results also indicate that copper(II) complexes 8–11 have square planar geometry.
Copper(II) complexes generally exhibit two different types of EPR spectra, isotropic and anisotropic. Cu(II) complexes 8, 9 and 11 and their EPR data supported the square-planar geometry.
The data of thermogravimeric analysis (TGA) were discussed. The thermal stability of the synthesized complexes and the nature of solvent molecules to be outside or inside the inner coordination sphere of the metal were discussed.
The suggested formulas were well-matched with the obtained results.
II- Antitumor Activity of the ligand and some of its metal complexes:
This section presents the importance of the prepared ligand and some of metal complexes as antitumor agents.
The possible antitumor activities of Cu (II), Co(II), and Ni(II) complexes were estimated through determination their effect on liver enzymes, albumin, Ki67 and P53 expression . Results revealed that administration of Cu(II), Co(II), and Ni(II) complexes to the mice led to improvement in the hepatic function as well as liver histology. Moreover, treatment with these complexes led to a marked decline in the Ki67 expression in hepatic cells and increase level in p53.
Overall, the antitumor activity of the newly synthesized metal complexes against EAC solid tumors was proved to be mediated by the inhibition of Ki67 and induction of P53 proteins .