الفهرس 
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Abstract
This Thesis Consists Of The Following Parts:
I. Introduction:
In This Section, A Literature Review About Inflammation, Anti-Inflammatory Targets, Various Biological And Pharmacological Activities Of Indole Nucleus And Certain Synthetic Approaches For Indole Derivatives Were Presented.
II. Aim Of The Work:
It Included The Research Objectives And The Major Aims That Directed The Theoretical And Practical Work.
III. Results And Discussion:
1. Chemistry
In This Part, Various Experimental Methods And Conditions Of Reactions Adopted For The Preparation Of The Designed Compounds Were Discussed. In Addition, It Dealt With The Confirmation Of The Newly Synthesized Compounds By Different Methods Including Elemental Analysis, Infrared, 1H NMR And 13C NMR Spectral Data.
2. Biological Study
This Part Discussed The Results Obtained from The Study Of Synthesized Compounds Against Different Biological Activities As Illustrated Below:
2.1. In Vitro COX-1/COX-2 Inhibition Assay:
The Ability Of The New Compounds To Inhibit COX-1 And COX-2 Activities Was Determined Using COX Colorimetric Inhibitor Screening Kits. Compounds (Va-F, Viia-L, Xa-C, And Xia-C) Showed Good COX-2 Inhibitory Activity (IC50 = 0.35-0.10 µm) In Comparison With Indomethacin (IC50 = 0.49 µm) And Celecoxib (IC50 = 0.05 µm).
2.2. In Vivo Anti-Inflammatory Evaluation:
The Anti-Inflammatory Activity Of The New Compounds Was Evaluated Using ”Rat Paw Edema” Method. Compounds (Va-F, Viia-L, Xa-C, And Xia-C) Showed Good Anti-Inflammatory Activity (51.9-93.7% Edema Inhibition) In Comparison With Indomethacin (96.6% Edema Inhibition) And Celecoxib (94.7% Edema Inhibition).
2.3. Nitric Oxide Release Assay
The Amount Of NO Released from Compounds Xia-C Was Measured Using The Modified Griess Reagent In Phosphate Buffer Of Ph 7.4 In The Presence Of N-Acetyl Cysteine. The Amount Of NO Released from The Tested Compounds Was Measured Relative To NO Released from Standard Sodium Nitrite Solution. Compounds Xia-C Were Found To Release Moderate Amounts Of NO Compared To The Sodium Nitrite Standard Solution.
2.4. Antimicrobial Activity
Primary Antibacterial Study Was Conducted Against Five Bacterial Strains: E. Coli, K. Pneumoniae, A. Baumannii, P. Aeruginosa And S. Aureus (MRSA). Compounds Viia, Viih, Viij, Ixc And Ixi Showed Good Antimicrobial Activity. In Addition, The Antifungal Activity Was Examined Against C. Albicans And C. Neoformans. Compounds Ixc And Ixi Showed A Good Antifungal Activity.
Compounds Viia, Viih, Viij, Ixc And Ixi Were Evaluated For Their Cytotoxicity Against A Human Embryonic Kidney Cell Line And Hemolysis Of Human Red Blood Cells. Most Of Tested Compounds Were Safe And Non-Toxic.
2.5. In Vitro Antiproliferative Activity
It Included The Screening Results Of Ten selected Compounds Against NCI 60 Cell Line Panels (Six Cell Lines Of Leukemia, Nine Cell Lines Of Lung Cancer, Six Cell Lines Of CNS Cancer, Seven Cell Lines Of Colon Cancer, Eight Cell Lines Of Melanoma, Six Cell Lines Of Ovarian Cancer, Eight Cell Lines Of Renal Cancer, Two Cell Lines Of Prostate Cancer And Eight Cell Lines Of Breast Cancer) Representing On Full Nine Human Systems As Leukemia, Melanoma And Cancers Of Lung, Colon, Brain, Breast, Ovary, Kidney And Prostate, According To Their Applied Protocol. Compounds Viii And Ixh Showed Potent Antiproliferative Activity.
3. Molecular Modeling
The Molecular Modeling Study Involved The Essential Binding Features Of The Target Compounds To COX-2 Isozyme To Understand The Nature Of The Interaction With Amino Acid Of COX-2 Active Site, A Molecular Modeling Study Was Performed Using Crystal Structure Data For COX-2 (PDB: ID 3LN1) Which Is Obtained from Protein Data Bank And Compared To The Docking Results Of The Parent Co-Crystallized Ligand Celecoxib.
IV. Experimental:
1. Chemistry
This Part Presented The Practical Procedures Used For The Synthesis Of The Reported And New Intermediates As Well As The New Final Compounds. Also, It Summarized Their Spectral And Elemental Data.
The Following Compounds Were Synthesized:
Reported Intermediates:
• 2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Iva).
• 5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Ivb).
• 5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Ivc).
Newly Synthesized Intermediates:
• 2-(4-(Methylsulfonyl)Phenyl)-1H-Indole-3-Carbaldehyde (Via)
• 5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole-3-Carbaldehyde (Vib)
• 5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole-3-Carbaldehyde (Vic)
Newly Synthesized Final Compounds:
Include 33 New Compounds Classified Into Five Series.
The First Series Included:
• 1-Benzyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Va)
• 1-(4-Chlorobenzyl)-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Vb)
• 1-Benzyl-5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Vc)
• 1-(4-Chlorobenzyl)-5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Vd)
• 1-Benzyl-5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Ve).
• 1-(4-Chlorobenzyl)-5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Vf).
The Second Series Included:
• 3-((2-(4-Fluorophenyl)Hydrazono)Methyl)-2-(4-(Methylsulfonyl) Phenyl)-1H-Indole (Viia)
• 2-(4-(Methylsulfonyl)Phenyl)-3-((2-(P-Tolyl)Hydrazono)Methyl)-1H-Indole (Viib).
• 2-(4-(Methylsulfonyl)Phenyl)-3-((2-(4-(Methylsulfonyl)Phenyl) Hydrazono)Methyl)-1H-Indole (Viic).
• 4-(2-((2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)Methylene) Hydrazinyl)Benzenesulfonamide (Viid).
• 5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-3-((2-(4-(Methylsulfonyl) Phenyl)Hydrazono)Methyl)-1H-Indole (Viie).
• 4-(2-((5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazinyl)Benzenesulfonamide (Viif).
• 3-((2-(4-Fluorophenyl)Hydrazono)Methyl)-5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Viig).
• 5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-3-((2-(P-Tolyl)Hydrazono) Methyl)-1H-Indole (Viih).
• 5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-3-((2-(4-(Methylsulfonyl) Phenyl)Hydrazono)Methyl)-1H-Indole (Viii).
• 4-(2-((5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazinyl)Benzenesulfonamide (Viij).
• 5-Fluoro-3-((2-(4-Fluorophenyl)Hydrazono)Methyl)-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole (Viik).
• 5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-3-((2-(P-Tolyl)Hydrazono) Methyl)-1H-Indole (Viil).
The Third Series Included:
• 2-((2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)Methylene) Hydrazine-1-Carboxamide (Ixa).
• 2-((2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)Methylene) Hydrazine-1-Carbothioamide (Ixb).
• 2-((2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)Methylene) Hydrazine-1-Carboximidamide (Ixc).
• 2-((5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazine-1-Carboxamide (Ixd).
• 2-((5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazine-1-Carbothioamide (Ixe).
• 2-((5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazine-1-Carboximidamide (Ixf).
• 2-((5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazine-1-Carboxamide (Ixg).
• 2-((5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazine-1-Carbothioamide (Ixh).
• 2-((5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl) Methylene)Hydrazine-1-Carboximidamide (Ixi).
The Fourth Series Included:
• 5-Chloro-2-(2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)-1H-Benzo[D]Imidazole (Xa).
• 5-Chloro-2-(5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)-1H-Benzo[D]Imidazole (Xb).
• 5-Chloro-2-(5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indol-3-Yl)-1H-Benzo[D]Imidazole (Xc).
The Fifth Series Included:
• 2-(4-(Methylsulfonyl)Phenyl)-1H-Indole-3-Carbaldehyde Oxime (Xia).
• 5-Fluoro-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole-3-Carbaldehyde Oxime (Xib).
• 5-Methyl-2-(4-(Methylsulfonyl)Phenyl)-1H-Indole-3-Carbaldehyde Oxime (Xic).
2. Biological Study
This Section Deals With The Laboratory Detailed Materials And Procedures Used In The Evaluation Of The Biological Activities Of Synthetic Compounds.
V. References:
This Part Included 149 References Covering The Period 1927-2018.
VI. Arabic Summary.