الفهرس Only 14 pages are availabe for public view
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Abstract
The thesis consists of two parts in each of which the main objective was generally developing novel synthetic chemical entities, as well as the exploration of their activity through certain specific biological systems.
In part one, a new series of 1-substituted-4-(2-chloroethyl)semicarbazide derivatives (CESCs) were designed, synthesised, and evaluated for their cytotoxic activity against two cell lines, human brain carcinoma and human liver carcinoma. This series of compounds represents a novel class that has not been estimated for cytotoxic activity before. 4-(2-Chloroethyl)-1-[(1H-indol-3-yl)methylene] semicarbazide (85) showed the highest cytotoxic activity among the synthesized new compounds against the assigned cell lines and consequently, it is recommended for further optimization and mechanism of action studies. The introduction of part one describes the classification of anticancer drugs under two major classes; classical cell killers and novel targeted cancer therapies. The introduction also describes in details a variety of antimitotic agents as anticancer drugs. After introduction, the aim of work describes the target of the study and includes the schemes illustrating the synthesis of the new proposed compounds. The theoretical discussion of part one illustrates the historical background of urea containing anticancer drugs. It then discusses the procedures exploited to synthesize the novel proposed chemical compounds, analytical methods used in structural elucidation of the new compounds like elemental analysis, IR spectroscopy, proton nuclear magnetic resonance, and mass spectroscopy. Finally the theoretical discussion describes the derivatization of relationships between the chemical structure of the new compounds and their cytotoxic activity against both human brain and human liver carcinoma cells. The experimental part of part one includes the procedures exploited for synthesis of the new compounds in details as well as the physical constants and spectroscopic data of the new compounds. The experimental part also describes the Sulfohodamine B method used for determining the cytotoxic activity of the proposed derivatives.