الفهرس 
Aim of The WorkOnly 14 pages are availabe for public view
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Abstract
The original work of the thesis is subdivided into two main parts : Part 1. Chemical reactivity studies : The present study seeks to synthesize some heterocyclic compounds with a fixed space shape based on benzo[b]pyronate nucleus of potential medical interest. This study is divided into two parts as follows : For the synthesis of heterocyclic compounds with biological activity by using 7-hydroxy-spiro[2,1/-cyclohexane]-4-on 1 as a precursor (starting material) to give the alkylated derivatives 2-4. While by reacting with Mannich reaction to give two other derivatives 5, 6, and it is reacted with phenyl diazonium salt to give a diazonium derivative 7. The activity range of compound 1 was expanded by introducing an ethyl acetate group by reacting with ethyl bromoacetate via a phenolic hydroxyl group to produce an ester derivative 8, which is treated with hydrazine hydrate to give hydrazide derivative 11. Hydrazide 11 has been used as a second important raw material for the synthesis of many 12-16 heterocyclic derivatives. On the other hand, the activity of compound 2 produced from the precursor 1 was tested against many nucleophilic reagents to give the derivatives 17-25. The cyano-acetohydrazone derivative 22 was reacted with several reagents to give the compounds 26-33. Condensation reactions of the starting compound 3 with hydroxylamine hydrochloride, hydrazine and phenyl hydrazine efficiently yielded oxime derivatives 40, hydrazone 41 and phenylhydrazone 42, respectively. The indole derivative 43 was prepared by subjecting compound 42 via Fisher reaction. Furthermore, the reaction of compound 42 with phenyl isothiocyanate gave a thiazolidine derivative 44. Part 3. Biological Evaluation and computational studies. First : Computer study - By conducting Docking’s studies on derivatives 7, 11, 19 and 27, these compounds showed an appropriate match in the binding sites with some important amino acids for the microbes under study through the formation of strong hydrogen bonds that stimulate anti-bacterial and anti-fungal activity. Moreover, some biological activities of the compounds prepared using PASS online software were predicted as antimicrobials, anti-infectives and anti-tumors, and their activity was also tested as anti-microbials for some single-celled organisms. Second : Biological survey of compounds as antitumors, the toxicity of compounds constructed as antitumor agents against hepatocellular carcinomas HePG-2 was evaluated using an in vitro system using doxorubicin as a reference drug. The results showed that the derivative of amino-oxazole 32 was the most effective compared to doxorubicin. Moreover, hydrazide 11 and thioseme carbazone 34 showed similar activity to that of the reference drug. Also, compounds 7, 16, 28 and 42 showed good activity. As for the rest of the compounds, it showed less effectiveness than the reference.