الفهرس 
Oxidation state and coordination chemistry
Results and DiscussionOnly 14 pages are availabe for public view
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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
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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: