Thesis (Ph.D.) - Cairo University - Faculty of Science - Department of Organic Chemistry

The first project involves the reaction of 7,9-di(4-methoxyphenyl)-2-thioxo-2,3- dihydropyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(1H)-one (3) or its 2-methylthio derivative 4 with hydrazonoyl halides 5a-l in dioxane under reflux, in the presence of triethylamine, yielded the corresponding pyrido[3',2':4,5]thieno[3,2-d][1,2,4]triazolo [4,3-a]pyrimidin-5(1H)-ones 8a-l. The structure of compounds 8a-l was further confirmed by the reaction of 3 with the appropriate active chloromethylenes 11a-c followed by coupling the products with benzenediazonium chloride to afford the azo- coupling products 6b, f, j which converted in situ to 8b, f, j. 2-Hydrazinylpyrido [3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-one (13) was prepared and condensed with different aldehydes 14a-f to give the corresponding hydrazone derivatives 15a-f. Oxidative cyclization of the hydrazone derivatives 15a-f gave the corresponding triazolo[4,3-a]pyrimidin-5(1H)-one derivatives 16a-f. The antimicrobial activity of some selected products was evaluated using well diffusion agar assay and MIC determination. The results proclaimed that compounds 8f and 15f showed excellent activity against Gram positive bacteria while compound 15d showed the highest activity against Gram negative bacteria. Moreover, compounds 15b, 8d, 8e, 8c, 8l and 8j exhibited significant antifungal activity compared with reference drug. In addition, the anti-cancer activity of the synthesized products against different cancer cell lines was determined and the results revealed promising activity of compounds 12a, 12b and 12c, compared with reference drugs. Moreover, compound 12c was the most active against MCF-7, HepG-2, HCT-116 and HeLa with IC50 values of 0.51, 0.72, 0.95 and 0.95, respectively, as compared with doxorubicin as positive control

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