الفهرس | Only 14 pages are availabe for public view |
Abstract In the present study there is a brief literature review covering the most important biological activities and the general methods for synthesis of pyridine, pyrazole, thiazole and dihydrothiazolone derivatives. Novel pyrazoline derivatives Va-g , VIa-g , IXa-c , Xa-c and XIa-c have been synthesized starting from new α,β-unsaturated ketones IVa-g and VIIIa-c via reaction with hydrazine hydrate in ethanol and acetic acid and thiosemicarbazide (schemes 1,2).N-Thiocarbamoyl pyrazoline derivatives XIa-c used as key intermediate for the synthesis of some new 2-pyrazolylthiazoles XIIa-l via cyclization using phenacyl bromide derivatives (scheme 3) .Moreover,new nicotinamide derivatives containing thiosemicarbazone moiety XIIIa-d were obtained by refluxing equimolar amounts of N-(4-acetylphenyl)nicotinamide III and the corresponding thiosemicarbazide derivatives (scheme 4) . Furthermore the nicotinamide derivative with thiosemicarbazone moiety XIIIa was cyclized to either thiazolyl nicotinamide derivatives XIVa-d,thiazolyl-4-(5H)-one-2-yl nicotinamide XV and nicotinamidothiazole carboxylate XVI through their reaction with phenacyl bromide derivat ives , ethyl bromoacetate or ethyl 2- chloroacetoacetate, respectively .(Scheme 5). Furthermore, theoretical discussion and detailed survey for the experimental results attained with an interpretation of data. The chemical structure of the newly synthesized compounds was confirmed by IR, 1HNMR, 13CNMR, mass spectrometry and elemental analysis.The antimicrobial activity evaluation showed that most of the newly synthesized compounds exhibited promising antibacterial as well as antifungal activities. On the other hand, some of the new compounds were screened for cyclooxygenase I and II (COX-I and COX-II) inhibition assays using Celecoxib ,Diclofenac and Indomethacin as standards,Moreover their anti-inflammatory and ulcerogenic activities were carried out using Celecoxib and Indomethacin as reference drugs. The results obtained clearly focus the significance of compounds XIIa, XIIb, XIIe, XIIj, XIIk, XIIl and XV as selective COX-II inhibitors, However,their efficacies were associated with lower gastric ulcerogenicity compared to Indomethacin. Furthermore, some selected samples of the newly synthesized compounds were evaluated for their anticancer activity against breast carcinoma (MCF-7) and colon carcinoma (HCT-116) cell lines, Imatinib was used as positive control. The anticancer activity showed that compounds Vc and VIc were the most active against the two cell lines. Molecular docking studies were performed in order to rationalize the obtained biological results. |