الفهرس 
introduction
cancer therapyOnly 14 pages are availabe for public view
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Abstract
Abstract:
In this thesis a series of novel 4-substituted quinazoline derivatives was rationally designed, synthesized and biologically evaluated for their anticancer activity. The sixteen synthesized compounds IVa-f, Va-d, VIa-d and VIIa,b were evaluated for their antitumor activity against certain breast and hepatic cell lines at National Cancer Institute (NCI, Egypt). Eight of these compounds IVc, IVf, Vc, VIa-d, VIIb were selected due to their promising activity against the cell lines to be tested in vitro against VEGFR2 inhibition in KINEXUS cooperation, Canada. Compound VIa show marked activity against VEGFR2. The obtained results were clarified using molecular modeling study.
The presented thesis comprises the following chapters:
1- Introduction:
It contains a survey covering the definition of cancer, its causes, and how it is formed, also through this section cancer therapy strategies are fully explained with examples, especially kinases, where their structures, types and inhibitors are fully explained.
2- Rationale and design:
In this section quinazoline derivatives have been synthesized hoping to act as VEGFR-2 inhibitors. The design depends on exploration of the previous revealed SAR studies, identification of the key interactions with the binding site and bioisosteric modifications of the reference compound. Synthesis of target compounds was carried out adopting the chemical pathway outlined in schemes (1-2).
3- Results and Discussions:
This part contains the theoretical discussions for the obtained results.
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3.1 Chemistry
It includes different methods of synthesis that are reported in literature which were used for the synthesis of the intermediate and final compounds. Also, the final compounds were discussed regarding their physical and the spectroscopic data.
3.2 Biological evaluation
The biological evaluation was accomplished by testing both anticancer activity and enzyme inhibition activity. The anticancer activity of the sixteen synthesized compounds was evaluated at the national cancer institute (NCI), Egypt. They were tested against two cancer cell lines, hepatic tumour cell line (HEPG2), and breast cancer cell line (MCF-7). The results of some compounds showed significant anti-cancer activity. Eight compounds were evaluated for their VEGFR-2 inhibition activity. The evaluation was performed in KINEXUS Corporation, Canada.
3.3 Molecular Modeling:
The design was based on the molecular modeling simulation; by direct molecular docking study using Glide program then further explanations were done using discovery studio software.
4- Experimental:
This part explains the laboratory detailed procedures in synthesis of the chemical compounds and record of the physical and spectral properties of the new products.
In addition, the biological evaluation procedure was mentioned.
The chemistry section comprises the synthesis of the following:
Reported starting materials :
4-Aminoquinazoline (I)
Abstract
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New intermediate:
2-Chloro-N-quinazoline-4-yl-acetamide (II)
2-Bromo-N-quinazolin-4-yl-propionamide (III)
The study involves the synthesis of the following new targeted compounds:
4-Chloro-2-[(quinazolin-4-yl-carbamoylmethyl)-amino]-benzoic acid (IVa)
2-Indol-1-yl-N-quinazolin-4-yl-acetamide (IVb)
2-(4-Phenyl-piperazin-1-yl)-N-quinazolin-4-yl-acetamide (IVc):
2-Morpholine-4-yl-N-quinazolin-4-yl-acetamide (IVd)
2-[4-(4-Nitrophenyl)-piperazin-1-yl]-N-quinazolin-4-yl-acetamide (IVe)
2-[4-(2-Methoxyphenyl)-piperazin-1-yl]-N-quinazolin-4-yl-acetamide (IVf)
4-Chloro-2-[1-(quinazolin-4-yl-carbamoyl)-ethylamino]-benzoic acid (Va)
2-Indol-1-yl-N-quinazolin-4-yl-propionamide (Vb)
2-(4-Phenyl-piperazin-1-yl)-N-quinazolin-4-yl-propionamide (Vc)
2-Morpholin-4-yl-N-quinazolin-4-yl-propionamide (Vd)
1-(4-Chlorophenyl)-3-quinazolin-4-yl-urea (VIa)
1-(3-Chlorophenyl)-3-quinazolin-4-yl-urea (VIb)
1-(2-Chloroethyl)-3-quinazolin-4-yl-urea (VIc)
1-(2-Chloroethyl)-3-quinazolin-4-yl-thiourea (VId)
1-(2-Morpholin-yl-ethyl)-3-quinazolin-4-yl-urea (VIIa)
1-[2(4-Phenyl-piperazin-1-yl)-ethyl]-3-quinazolin-4-yl-urea (VIb)
5- Conclusion:
This part includes summary of the thesis.
Abstract
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6-References:
160 recent references were recorded showing the literature survey for this r