Basic Informations

C.V

Master Title

“Synthesis of certain 8-quinolyloxy and/or carbocyclic nitrogenous compounds for microbiological testing"

Master Abstract

The present thesis comprises a survey covering the biological importance of 8-hydroxyquinolines and the carbocyclic p-aminobenzoic acid and salicylic acid derivatives. The study involves esterification of p-aminobenzoic acid with ethanol to give benzocaine (I) which was diazotized then reacted with salicylic acid to yield the azo derivative II. Hydrazinolysis of the ester II resulted in the hydrazide III. Condensation of the latter with some aromatic carbonyl compounds afforded the arylidene derivatives IVa-l. Also, reacting the hydrazide III with certain acid anhydrides led to the substituted amide derivatives Va-c.

PHD Title

" synthesis of fused thienopyrimidines of biological interest"

PHD Abstract

Abstract This thesis comprises four chapters. The first one is an introduction which consists of a brief literature survey about different methods to synthesize thieno[3,2-d]pyrimidine and thieno[3,4-d]pyrimidine containing compounds in addition to an account on their cytotoxic activities. The second chapter clarifies the objectives of the work and the Schemes designed for the preparation of the new required target compounds. The third chapter deals with the theoretical discussion of the experimental work for the preparation of the starting materials Ia&b, IIa-d and the key intermediates IIIa-d, XVa&b, in addition to the target new compounds IVa-d, Va&b, VIa&b and the new hydrazides VIIa&b which on condensation with aromatic aldehydes furnished VIIIa-f. Reacting the key intermediates IIIa-d with orthoesters, formamide, cyclohexanone and aromatic aldehydes afforded IXa-f, XIIa&b, XIIIa&b and XIVa-f, sequentially. Moreover, reaction of IXa&b with hydrazine hydrate gave Xa&b that underwent cyclization to triazole derivatives XIa-d upon treatment with different orthoesters. Reacting XVa&b either with the suitable alkyl halide or POCl3 yielded XVIa-g and the chloro derivatives XVIIa&b, respectively. The latter compounds converted to XVIIIa&b which, in turn, cyclized with SOCl2 to afford XIXa&b. The structure elucidation of the new compounds was supported by element analysis, IR, 1H-NMR and mass spectral data. Additionally, a brief account on the docking study was explained through the binding conformations in comparison with the experimental results. The fourth chapter consists of the experimental part of this thesis which contains the detailed procedures used for the synthesis of the starting compounds Ia&b and IIa-d, the key intermediates IIIa-d and XVa&b in addition to the target new compounds IVa-d, Va&b, VIa&b, VIIa&b, VIIIa-f, IXa-f, Xa&b, XIa-d, XIIa&b, XIIIa&b, XIVa-f, XVIa-g, XVIIa&b, XVIIIa&b and XIXa&b. This chapter clarifies the physical properties in addition to the detailed data obtained from element and spectral analysis of the newly synthesized compounds. It also includes the in-vitro anticancer activity of fifteen compounds of the novel target compounds compared with doxorubicin as a reference anticancer agent. The results revealed that nine of the test compounds showed enhanced anticancer activity than doxorubicin. Finally, this chapter demonstrates the correlation between the results of the molecular docking study and the anticancer evaluation. Indeed, compound XIIa showed the highest energy score (-26.43 Kcal/mol) and exhibited the most potent in-vitro cytotoxic activity with IC50 = 2.04 µM.