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Abstract The master thesis include aim of the work and three main chapter Aim of the work The work of the present thesis will be oriented to prepare and characterized newly synthesized ligands and their vanadium complexes in order to use as anti-diabetic drugs. I-Introduction This chapter includes an overview of previous researches for complexes of Schiff base ligands and their vanadium complexes and also to study their biological activity as antidiabetic. II-Experimental part The first part of this chapter will be oriented to synthesis new ligands and their vanadium complexes. The structure will be investigated using different techniques such as: elemental, thermal and spectral analyses (IR, 1H- NMR, UV-Vis, Mass and ESR) as well as magnetism and molar conductances. The second part is to study: 1-The effect of newly synthesized complexes (in vivo) when given once orally to overnight food deprived rats given oral glucose load (oral glucose tolerance test). 2-Complexes with promising effects will be tested in streptozotocin (STZ)-induced hyperglycemia in rats (several dose levels, single or repeated administration). 3-preleminary safety studies will be carried out on the most promising compounds. - The third part includes histopathological examination of pancreatic & kidney tissues taken from animal groups of the second part using routine hematoxylin and eosin staining to detect the effect of the used vanadium chelates on these tissues. III-Results and discussion This chapter includes characterization of the ligands and their vanadium complexes. Synthesis of the ligands (1)-(10) is illustrated in schemes (1), (2), (3), (4) and (5). First, dimethyl tartrate was used as starting material in the formation of ligands (1), (2), (4) and (8). As it reacted with hydrazine hydrate followed by salicylaldehyde, hydrazine hydrate only, o-phenylenediamine only or o-phenylenediamine followed by 3-(hydroxyimino)pentane-2,4-dione yielded ligands (1), (2), (4) and (8) respectively scheme. 2. Ligand (3) was prepared by adding equimolar amounts of ethyl chloroacetate and aniline. The mixture was refluxed with hydrazine hydrate and salicylaldehyde (scheme.3). Ethyl chloroacetate with methyl p-hydroxybenzoate sodium salt were considered the synthons for preparing ligands (5) and (6). In ligand (5), hydrazine hydrate was added in second step but for ligand (6) ophenylenediamine was added. The last step, 3-(hydroxyimino) pentane-2, 4-dione was added for both ligands (scheme.4). Ligand 7 was prepared by adding o-phenylenediamine to 3-(hydroxyimino) pentane -2, 4-dione . Finally, ligands (9) and (10) were prepared by refluxing equimolar amounts of ethyl acetoacetate and 1,2-dibromoethane and o-aminophenol or o-amino benzoic acid respectively(scheme. 5) . All ten new vanadium complexes were tested on rats with OGGT test to perform the best effect of complexes on glucose level with different doses , after acute and chronic administration of the complexes to diabetic rats .The result, we found that complexes (1) and (8) decrease glucose level and after histopathological examination for liver and kidney we found no toxic effect. |