الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Bisphosphonates are characterized by the [P-(R1)C(R2)-P] structure, are class of drugs that slow down or prevent bone loss. They inhibit osteoclasts (responsible for bone resorption), and allow osteoblasts (bone building cells) to be more effective; i.e., improving the bone mass. Moreover, Bps are considered as anticancer drugs that cause bone damage. Since nitrogen-containing bisphosphonates inhibit the mevalonate pathway in osteoclasts and macrophage. This thesis consists of three main chapters are; Chapter 1 (Introduction): presents an overview of the pertinent literature. Chapter 2 (Experimental): describes the methods and measurements employed in this study as well as the methods of preparation of the complexes and the conditions employed for biological applications Chapter 3 (Results and Discussion): dealing with the characterization of the isolated complexes, DNA studies, which were carried out by Gel Electrophoresis and titrations using UV-Vis spectroscopy, in vivo anti-osteoprosis activity, and in vitro anticancer activity and Drug delivery. Introduction is a literature survey covered bisphosphonates and their different structures, nitrogenous and non-nitrogenous bisphosphonates, molecular structure, their medical usag. Also, this part contains the bisphosphonates’ mechanism of action as drugs. In addition, this research review involves bisphosphonates (Bps) and alendronate (HAld-), and their transition-metal complexes. The anti-osteoporosis activity, anti-cancer activity and DNA interaction of some bisphosphonate metal complexes are also discussed. Also drug delivery on HAnp is discussed. Experimental describes the synthetic methods and the physical measurements applied in this study. The details of the preparation of the complexes of silver(I), platinum(II) and palladium(II) complexes with sodium alendronate (NaHAld), [Pd(Ald)(H2O)2], [Pd2(bpy)2(Ald-2H)], [M2(DACH)2(Ald-2H)], [Pd2(apy)2(Ald-2H)], [Ag2(apy)(Ald)], [M(HAld)2] and [Pd2(Ald)(HAld)Cl(H2O)] {(M(II) = Pd, Pt); DACH = trans-1,2-diaminocyclohexane, apy = 2-aminopyrimidine}. Moreover, the conditions for the anti-osteoporosis, anticancer, in vitro DNA studies and Drug delivery activities are included. Results and Discussion dealing with the characterization of the new transition-metal complexes using various spectroscopic (IR, Raman, 1H-, 13C- and 31P-NMR, UV-vis, mass, SEM) studies, together with elemental analysis, molar conductivity, magnetic susceptibility and thermal measurements. This study is reported the synthesis of new Ag(I), Pd(II) and Pt(II) complexes with sodium alendronate; [Pd(Ald)(H2O)2], [Pd2(bpy)2(Ald-2H)], [M2(DACH)2(Ald-2H)], [Pd2(apy)2(Ald-2H)] , [M(HAld)2], [Pd2(Ald)(HAld)Cl(H2O)] {(M(II) = Pd, Pt); DACH = trans-1,2-diaminocyclohexane, apy = 2-aminopyrimidine} and [Ag2(Ald)(apy)]. They were full characterization using IR, Raman, 1H, 13C and 31P NMR, UV-visible, mass, SEM spectra, elemental analysis, molar conductivity, and TGA measurements. In the binuclear complexes, [Pd2(bpy)2(Ald-2H)], [M2(DACH)2(Ald-2H)], [Pd2(apy)2(Ald-2H)], [M(HAld)2] and [Pd2(Ald)(HAld)Cl(H2O)], the bisphosphonate moiety (Ald-2H) is acting as a bridging ligand between two [ML2]2+ (M(II) = Pd, Pt; L = DACH, apy) units. In the complex, [Ag2(apy)(Ald)], Ald-2, acts as binegative bidentate, while in the complexes, [M(HAld)2], the ligand acts as mononegative bidentate. The complex, binuclear [Pd2(bpy)2(Ald-2H)] exhibits high cytotoxicity against the human prostate (DU 145) and breast (MDA-MB231) cancer cell lines was tested, in which cisplatin; widely used anticancer agent. This results encourage us to study the in vitro adsorption and desorption of the drug, [Pd2(bpy)2(Ald-2H)], onto the surface of HAnp and its release using UV-visible spectroscopy. Moreover, it appears that The release of the neutral drug, [Pd2(bpy)2(Ald-2H)], takes place through complete cleavage of the Pd-bisphosphonate bond. The obtained results showed that HAnp and antitumor drug can be selected in such a way that the bioactivity of the drug–HAnp conjugate could be tailored for specific therapeutic applications. The complexes, [Pd2(DACH)2(Ald-2H)], [Pt2(DACH)2(Ald-2H)], [Pd(HAld)2] and [Pd2(Ald)(HAld)Cl(H2O)], exhibited low to moderate CT-DNA interaction affinity, in a partial intercalation mode with binding constant (Kb) 1.8 x 104, 2.21 x 106, 2.20 x 106 and 1.59 x 106 M-1, respectively. The low binding ability of these complexes may be owing to the steric hindrance around the metal ions coordinated to Ald-2H4-, Ald2- or HAld- moieties. NaHAld and its complexes, [Pt2(DACH)2(Ald-2H)], [Pd2(DACH)2(Ald-2H)], [Pd2(Ald)(HAld)Cl(H2O)] and [Pd(HAld)2], have been evaluated as anti-osteoporosis agents based on histological observation and bone X-Ray. The binuclear Pt(II) complex shows remarkable results as a promising anti-osteoporotic agent.