الفهرس 
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Abstract
Heterocyclic compounds are organic molecules with diverse chemical characteristics and applications. They are often used in drug development to treat various conditions, including cancer. Researchers are exploring the development of novel heterocycle derivatives using chalcone as a building block precorsor and investigating their biological and industrial applications.
This thesis explores the formation of N-, S-, and O-containing heterocycles through Michael reactions of chalcone compounds. The compounds were characterized using spectral data and applications, including antioxidant activities, theoretical calculations, docking estimation, and insecticidal activities. Some compounds showed high antioxidant activity, while others showed good insecticidal activity, suggesting their potential as agrochemical insecticides against P. interpunctella and Nilaparvata lugens. This thesis was divided into three chapters:
The first chapter (Introduction): included a literature review of chalcones, including definition, properties, synthesis, reactions, structure-activity relationships, biological activities, and industrial applications. Additionally, it showed that chalcones are adaptable and can be used for the synthesis of several products for food, medicine, cosmetics, and skincare applications. Moreover, these compounds are fascinating, with numerous applications in the medicinal, pharmacological, and optical fields. The literature review also highlighted the reactions of chalcone to form different compounds that have a wide range of applications.
The second chapter (Experimental): showed a detailed description of all materials and experiments used in the synthesis of different compounds from chalcone compound. In this study, the reaction of chalcone with different active methylene derivatives, such as ethyl cyanoacetate, acetylacetone, and thioglycolic acid utilizing the pressurized microwave irradiation to afford the corresponding cyanopyridine, cyclohexanone, and thieno[2,3-c]chromen-4-one derivatives were illustrated. In addition, the formation of N-, S-, and O-containing heterocycles by the interaction of chalcone with nitrogen-containing nucleophiles such as hydrazine, hydroxyl amine, guanidine, urea, and aminothiourea was explored. Furthermore, epoxychalcone was formed by blocking the OH group in the hydroxy chalcone using an alkyl halide. As a nucleophilic reagent, hydrazine hydrate and phenyl hydrazine derivatives were used to perform nucleophilic reaction on epoxychalcone led to the formation of pyrazole compounds. Also, this chapter showed the procedures for forming imidazolone from the reaction of epoxychalcone with guanidine hydrochloride and urea.
This chapter was also explain the characterization data of the prepared conpounds such as: FT-IR, 1HNMR, 13CNMR, and mass spectrum. Also, it concerned with the spectra and the analysis of all studied compounds.
The third chapter (Results and discussion): included discussion of the chalcone as a simple scaffold compound and building block for a variety of biologically potent heterocyclic compounds. The formation of N-, S-, and O-containing heterocycles by the interaction of chalcone with nitrogen-containing nucleophiles such as hydrazine, hydroxyl amine, guanidine, urea, and aminothiourea was explored. Also, the activity of 1-(2-hydroxyphenyl)-3-(p-tolyl)prop-2-en-1-one towards different active methylene derivatives such as ethyl cyanoacetate, acetylacetone, and thioglycolic acid to afford the corresponding cyanopyridine, cyclohexanone, and thieno[2,3-c]chromen-4-one derivatives. Also, the reaction of hydroxy chalcone with hydrogen peroxide affords the corresponding chromen-4-one derivative. Furthermore, the formation of epoxy chalcone after block the hydroxy group in hydroxy chalcone to used as precursor to differtent heterocyclic compounds was discussed. Additionally, various applications for the generated heterocyclic compounds were used, including antioxidant activities, theoretical calculations, docking estimation, and Insecticidal activities. All these applications used to explore the activity of the formed heterocyclic compounds. Some of these compounds showed the highest antioxidant activity, indicating their potential as antioxidants. Another compounds also shown good insecticidal activities, indicating their potential as agrochemical insecticides against P. interpunctella and Nilaparvata lugens. This chapter was organized in four parts.
Part I
The first part was concerned with the chemistry reactions for developing new variety of heterocyclic systems from chalcone for biological screening and industrial applications.
The chalcone reacts with different active methylene derivatives such as ethyl cyanoacetate, acetylacetone, and thioglycolic acid under pressurized microwave irradiation at 70 oC with pressure to afford the corresponding cyanopyridine, cyclohexanone, and thieno[2,3-c]chromen-4-one derivatives, respectively. Also, the reaction of chalcone with hydrogen peroxide with stirring affords the corresponding chromen-4-one derivative. All the synthesized compounds were confirmed through spectral tools such as FT-IR, 1HNMR, 13CNMR, and mass spectrometry.
Also, the formation of N-, S-, and O-containing heterocycles by the interaction of chalcone with nitrogen-containing nucleophiles such as hydrazine, hydroxyl amine, guanidine, urea, and aminothiourea was explored. FT-IR, UV-visible, NMR, and mass spectrometric studies were used to confirm the heterocyclic compounds that were produced.
Furthermore, epoxychalcone was formed by blocking the OH group in the hydroxy chalcone using an alkyl halide. As a nucleophilic reagent, hydrazine hydrate and phenyl hydrazine derivatives were used to perform nucleophilic reaction on epoxychalcone led to the formation of pyrazole compounds. Also, imidazolone formed from the reaction of epoxychalcone with guanidine hydrochloride and urea. Generally, all the synthesized compounds were confirmed through spectral tools such as FT-IR, 1HNMR, 13CNMR, and mass spectrometry.
Part II
The second part was concerned with X-Ray single crystal and theoretical studies for several compounds. Single crystals of the studied compounds were prepared by slow evaporation at room temperature in a suitable solvent. A comparative study between X-ray single crystal and theoretical studies as well as Hirshfeld surface analysis of these crystals was also performed.
Single-crystal X-ray diffraction is a potent technique for crystalline solid material structure investigation that is frequently utilized in organic chemistry. It provides detailed information on a crystalline matter’s interior crystal lattice. It can identify crucial crystal information such as unit cell dimensions, bond lengths and angles, site order, etc.
Theoretical chemistry is a systematic description of chemical events in matter that employs physics and mathematics to describe the structures and interactions of atoms and molecules. Recent advances in Density Functional Theory (DFT) and computer capacity have transformed computational chemistry into a useful tool for investigating chemistry structure and reactivity. Based on physics concepts and mathematical techniques, it gives theoretical tools to rationalize chemical phenomena such as chemical bonds, spectroscopy, and chemical reactions.
Hirshfeld surface analysis is used to quantitatively investigate the noncovalent interactions that are responsible for crystal packing. It is an effective way to visualize and understand interactions between molecules in crystals.
Part ӀII
The third part was concerned with antioxidant and molecular docking analysis. This part examined the antioxidant activity of N-, S-, and O-containing heterocycles that formed from hydroxy chalcone by their ability to scavenge the artificial radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH), as well as their biological activity through molecular docking stimulation.
The molecular docking method can be used to simulate the atomic interaction between a molecule and a protein, allowing us to describe small molecule behavior in target protein binding sites as well as elucidate critical biochemical processes.
Among the investigated compounds 5, 8, 10, and 12, compound 12 showed the best antioxidant properties, exhibiting an IC50 of approximately 202.20 µM and being comparable to vitamin C (IC50 at 141.9 µM). The IC50 values of the remaining compounds are decrease to approach the value of vitamin C in the order of 8 > 10. The order of the property depends on the radical stability formed in the derivatives.
The radical scavenging properties of compounds 3, 14, 15, 17a-c, 19, 20, 22, 24, 26, 28, 30, and 32 were studied using a DPPH assay in methanol. It can be seen that all compounds, except for 15, 17a, 22, 24, 30, and 32, possess antioxidant properties. In particular, compound 14 showed the strongest antioxidant properties among all synthesized compounds with an IC50 of approximately 93.4 µM and comparable to those of vitamin C (IC50 " ~ " 141.9 µM). The IC50 values of the remaining compounds are decrease to approach the value of vitamin C in the order of 3> 26 > 17c > 17b > 20 > 28 > 19. Accordingly, compounds 3 and 14 exhibit greater DPPH radical scavenging capacity than vitamin C as a reference compound, indicating that they are useful as antioxidants.
On the other hand, among the investigated compounds 5, 8, 10, and 12, the biological activity of compound 12 was demonstrated through molecular docking stimulation using two proteins, PDBID: 1DH2 and PDBID: 3RP8, which showed that compound 12 possesses greater binding energy and a shorter bond length comparable with ascorbic acid. Also, the docking estimations of compounds 3, 14, 15, 17a-c, 19, 20, 22, 24, 26, 28, 30, and 32 were compatible with experimental results for these heterocyclic compounds evaluated with PDBID:3RP8. We concluded that the antioxidant activity was exhibited from hydrogen bonding interaction between the OH group of the phenyl ring with DPPH radical scavenger which is confirmed through docking investigation.
Part IV
The fourth part was concerned with the Insecticidal activity of the synthesized materials 37, 38, 39, 40, 41, 42 and 45. The insecticidal activities of compounds 37, 38, 39, 40, 41, 42 and 45 were measured against healthy late third instar larvae P. interpunctella and Nilaparvata lugens according to the standard test with a slight modification. Compounds 37, 39 and 45 showed 100% activities at 400 µg ml-1 and 50% (IC50) activities at 100 and 50 µg ml-1 respectively against both P. interpunctella and Nilaparvata lugens showed a good insecticidal activities. While compound 40 showed 93.3% activity respectively against P. interpunctella and 73.4 % Nilaparvata lugens at 200 µg ml-1.