الفهرس | Only 14 pages are availabe for public view |
Abstract The present thesis includes three main chapters with Arabic and English summaries as well as a list of references used in this study which focus on synthesis and characterization of novel Pt(IV) complexes as potential anticancer agents. Chapter 1: - Introduction This chapter contains an introduction about the coordination chemistry of platinum, platinum(II) based anticancer drugs and platinum(IV) prodrugs with a scientific literature survey on the Pt(IV) complexes bearing biologically active axial ligands. Chapter 2: - Experimental This section gives details of methods used for preparing novel Pt(IV) complexes based on cisplatin, oxaliplatin and carboplatin with naproxen and vitamin E succinate (α -TOS) as biologically active axial ligands. Spectral methods (1H NMR, 195Pt NMR, IR and ESI-MS) and elemental analysis were used for characterization of the structures of the ligands and their Pt(IV) complexes. High performance liquid chromatography (HPLC) technique was used to study the reduction reaction of the Pt(IV) complexes. The cytotoxicity of the ligands and their complexes was evaluated with the aid of MTT assay on breast cancer cells MCF7 & MDA-MD-231. Chapter 3: - Results and Discussion This chapter collects the results obtained and their discussion. It consists of two parts. Part I In this part, Seven novel Pt(IV) complexes based on cisplatin, carboplatin and oxaliplatin with naproxen as biologically active axial xvi ligand have been prepared and their structures were elucidated by different analytical and spectral methods. The rate of reduction of the Pt(IV) complexes to cisplatin have been studied using HPLC. The cytotoxicity of the complexes was also measured on a pair of tumor cell lines suitably selected for their sensitivity and resistance to cisplatin (breast cancer cells MCF7 & MDA-MD-231). The results show that: 1. The HPLC studies showed that the complexes release the axial ligand in presence of reducing agent such as ascorbic acid. 2. The cytotoxicity studies revealed that generally, all complexes were on average more cytotoxic than cisplatin especially in resistant cells (MDA-MD-231 cells). 3. Among all complexes, the dicarboxylato complex 2 bearing the most lipophilic benzoate ligand showed the highest in vitro antiproliferative activity and demonstrated significant decrease in cyclin D1 concentration. 4. The novel Pt(IV) complexes showed anti-inflammatory properties with remarkable NO inhibition which indicated their potential in reducing cancer associated with inflammation Part II Five Pt(IV) complexes based on cisplatin with vitamin E analog, α -tocopheryl succinate (α -TOS) as biologically active axial ligands have been prepared and their structures were elucidated by different analytical and spectral tools such as 1H NMR, 195Pt NMR, IR, ESI-MS and elemental analysis. The possible transformation of the complexes into their active Pt(II) compounds in the presence of a reductant was verified using HPLC. The cytotoxicity of the complexes was also measured on human breast tumor cell lines. The results obtained can be summarized as follows: |