الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2- acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment with both nitrogen and carbon nucleophiles, and yielded diverse heterocyclic scaffolds such as pyrazoline, thiazole, pyrimidine, pyran, and pyridine derivatives. The pyrazoline aldehyde derivative 7 was further derivatized to produce the hydrazide- hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which was exploited to synthesize derivatives of 2-oxo-2H-chromene-3- carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, and 3-(4-nitrophenyl)acrylohydrazide 16. All the newly synthesized compounds were characterized by melting point, elemental analysis, as well as FT-IR, 1H-NMR, and mass spectroscopy. Furthermore, these heterocyclic derivatives were screened for their antioxidant capacities using the DPPH radical assay. The results showed that compounds 5 and 10 are the most potent antioxidants with IC50 values 178, 177(μM), respectively. comparable to that of ascorbic acid which has IC50 value 148. Meanwhile, compounds 2, 12, 13, 14, 15, and 16 exhibited moderate antioxidant activities with IC50 values ranged from 266 to 291(μM). Thus, these heterocycles could emerge as promising antioxidant drugs for the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 5, 10, and ascorbic acid inside the active pocket of Human Peroxiredoxin 5 (1HD2).
Part two
The synthesis of the enamino nitrile-based thiophene moiety was effectively accomplished by reacting p-t-butyl cyclohexanone with malononitrile in the presence of sulfur and triethylamine, serving as a catalytic base. This process resulted in the formation of Compound 17, designated as enamino nitrile, compound 17 showcased versatile reactivity upon exposure to nitrogen and carbon nucleophiles. This characteristic reactivity resulted in the synthesis of diverse heterocyclic scaffolds, encompassing pyrimidine-thione, pyrimidine, and pyridine derivatives. Also, compound 17 was exploited to react with different aromatic aldehydes to afford the corresponding Schiff’s bases 25a-c. The pyrimidine-4(3H)-one derivative 19 was further derivatized to prepare the corresponding pyrimidine thione 29, namely, 7-(tert-butyl)-6,7,8,9- tetrahydrobenzo[4,5]thieno[3,2-d]pyrimidine-4(3H)-thione, which was allowed to synthesize derivatives of 4-hydrazinyl thieno[3,2-d]pyrimidine 30, and thieno[3,2-d]pyrimidin-4-yl)thio)acetate 31. Additionally, the synthesis of compound 32 is achievable by subjecting compound 17 to hydrolysis. Subsequently, derivative 32 underwent condensation with benzoyl chloride, and ethyl chloroformate, resulting in the formation of pyrimidin-4(3H)-one derivative 33, and pyrimidine-2,4(1H,3H)-dione derivative 34. Melting point, elemental analysis, FT-IR, 1H-NMR, and mass spectroscopy characterized all the newly synthesized compounds. Furthermore, the total antioxidant capacity (TAC) of these heterocyclic derivatives was evaluated to ascorbic acid. The findings revealed that compounds 17, 29, and 30 demonstrated significant antioxidant potency comparable to that of ascorbic acid. In contrast, compounds 18, 23, 25a-c, 28, 31, and 32 exhibited moderate antioxidant activities. This suggests the potential of these heterocycles as promising candidates for antioxidant drugs
in the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 17, 29, 30 and ascorbic acid inside the interactions of compounds 17, 29, and 30 with the Keap1 (Kelch-like ECH-associated protein 1) protein (PDB: 7C5E), compared to the co-crystallized ligand triethylene glycol (PGE) and ascorbic acid as a reference drug for antioxidants. DFT calculations and global descriptors were calculated for the most potent compounds to correlate the relation between chemical structure and reactivity.