الفهرس 
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Abstract
The present thesis deals with the design and synthesis of a new hybrids of N-allyl/phenyl 1,2,4-triazole/ chalcone/ indole and allyl/phenyl 1,2,4-triazole/ indole/oxime derivatives and evaluating of their anticancer activity. The thesis includes four main parts; introduction, scope of investigation, results & discussion and the experimental one.
1- Introduction chapter
The introduction chapter consists of four parts; The first part of introduction discusses the biological activities of indole including anticancer, antioxidant, antimicrobial, anticonvulsant, anti-inflammatory, antiviral and antitubercular activities. The second part takes a quick look up on the biological activities of chalcones including anticancer, antioxidant, anticonvulsant, anti-inflammatory, antiviral antimalarial, antibacterial, antituberculosis, antifungal, antidiabetic, antihyperlipidemic and antihypertensive activities. The third part involves the new update in biology of 1,2,4-triazole derivatives as antibacterial, antifungal, antimicrobial, antioxidant, analgesic, anticancer, anticonvulsant, antiviral and anti-inflammatory activities. The fourth part covers the chemistry and biological activities of NO donating oximes as well as its potential role as anticancer agent and introducing examples on new NO donating oximes which exhibit anticancer activity and have the ability to overcome the resistance to chemotherapy and refractoriness to conventional therapeutics which is one of the major challenges in the treatment of cancer.
2- Scope of investigation chapter
This chapter outlines the main objectives and rationale of this work, including the synthesis of target compounds, biological evaluation of the anticancer activity of the prepared compounds, and also indicating to the concept of combining indole moiety with chalcones and oximes in one compact structure in the purpose of synergism and/or reduce side effects.
3- Results and discussion chapter
This chapter deals with discussion of the obtained chemistry and biology results and it is subdivided into three main categories:
A- The first part; chemistry section:
Which includes description of the methods used for the synthesis of the intermediates of (A) series 1 including; compounds 2a-j, 3a-j, 1H-indole-3-carbaldehyde (4), 1H-indole-3-carboxylic acid (5), ethyl 1H-indole-3-carboxylate (6), 1H-indole-3-carbohydrazide (7), and 4-allyl/phenyl-5-(1H-indol-3-yl)-4H-1,2,4-triazole-3-thiol (8), and the final target compounds (9a-s). (B) series 2 including; compounds 2-((5-(1H-indol-3-yl)-4-allyl/phenyl-4H-1,2,4-triazol-3-yl)thio)-1-phenylethanone derivatives (10a-j) and their corresponding oximes (11a-j). Structures of the final compounds were confirmed by different spectroscopic technique including; 1H NMR, 13C NMR as well as elemental analysis.
B- The second part; Biology
The biology part, which is subdivided into three sections, the first section is concerned with screening of the anticancer activity of the synthesized compounds 9a-s, 10a-j and 11a-j by National Cancer Institute (NCI) according to the protocol of the drug evaluation Branch of the National Cancer Institute, Bethesda, USA. The in vitro anticancer screening was carried out against 60 cell lines of different nine cancer cell. Results revealed that the tested compounds exhibited from complete cell death to moderate and weak anticancer activity against tested cell lines. Moreover, six compounds 9a, 9e, 10h, 11h, 11i and 11j were selected for five dose assay. The tested compounds exhibited a remarkable and broad spectrum of antitumor activity with no selectivity towards the tested cancer cell lines.
The second section investigates the antiproliferative activity of compounds 9a-s on four different cell lines including; pancreatic cancer cell line (Panc-1), breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and epithelial cancer cell line (A-549) using doxorubicin as a reference drug. GraphPad prism software (GraphPad Software, San Diego, CA, USA) was used to estimate the median inhibition concentration (IC50) for all of the tested compounds. Compound 9d displayed the highest inhibitory activity among all of the tested compounds against most of the cancer cell lines with average IC50 of 1.137 µM compared to the reference drug doxorubicin (average IC50 = 1.136 µM).
The third section deals with rationalization of the cytotoxic activity of the most active compounds (9a-e, 9g, 9i, 9k, 9n and 9o) through assessment of their ability to inhibit EGFR and c-Met kinase enzymes. All of the tested compounds exhibited inhibition of EGFR and c-Met. Comparing to EGFR inhibitory activity of erlotinib (IC50 = 0.05 µM), compound 9d was found to be the most potent EGFR inhibitor with IC50 of 0.052 µM. While compound 9b showed the highest c-Met inhibitory activity with IC50 value of 4.70 µM compared to the reference drug Foretinib (IC50 value of 2.50)
C- The third part
The third part is concerned with a molecular docking study to evaluate the binding modes, orientations, and interactions of compounds 9d and 9b into the ATP binding sites of EGFR and c-Met using MOE software program. The results of docking studies of the selected compounds support that EGFR and c-Met inhibition are the mechanisms by which these compounds may exert their anticancer activity.