الفهرس 
AbstractOnly 14 pages are availabe for public view
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Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are considered the most widely used therapeutic class in the treatment of inflammation and relief of pain. The pharmacological effects of these drugs arise from their inhibition effect on cyclooxygenases (COXs). A wide variety of benzimidazothiazole derivatives is present in the literature with potential anti-inflammatory activity. In this study a new series of benzimidazothiazole derivatives have been synthesized in an attempt to have fewer side effects and more activity. Forty seven compounds were prepared by different synthetic routes, among them forty compounds are new. The structure of the prepared compounds was confirmed by spectroscopic techniques such as IR, NMR and mass spectroscopy. The tested compounds were evaluated for their anti- inflammatory activity, either in vitro through COX enzyme inhibition assay, or in vivo through carrageenan induced paw edema technique. Results approved that compounds 122 and 92 represented the most active ones with % inhibition 73.08, 72.64 for COX-1, and 88.03, 87.75 for COX-2, respectively. In addition, all the synthesized compounds exhibited low IC50 values in comparison with naproxen and celecoxib indicating their potency. The ADMET analysis of the tested compounds was also performed, in addition the molecular modeling studies that included alignment, surface area electrostatic maps and Lipinski’s rule of five were also performed. The present thesis deals with the synthesis of new benzimidazothiazole derivatives to be tested for their anti-inflammatory effect. The content is divided into five parts, in addition to the Arabic summary. Part 1: The introduction: discusses the classification of anti-inflammatory drugs based on their chemical structure and their target. This part also includes different examples from recent literatures describing the anti-inflammatory effect of different benzimidazothiazole derivatives. Part 2: The research objectives: discusses the major aims that direct the theoretical and practical work. Part 3: The theoretical discussion of the experimental work: illustrates the different possible conditions for the preparation of the desired compounds. It also demonstrates the results of in vitro enzyme assay of the desired compounds against both COX-1 and COX-2 enzymes. In addition, it describes the results of in vivo anti-inflammatory activity in rats. Furthermore, the new analogs were studied for the prognosis of Lipinski’s rule of five, toxicological properties, and pre-ADMET criteria. Results articulated that all investigated compounds have one or zero violation of Lipinski’s rule. Part 4: The experimental work: includes the synthetic procedures of the designed compounds and the adopted procedure of in vitro enzyme assay and in vivo assay for anti-inflammatory screening. The structures of the newly synthesized compounds were confirmed by IR,1H NMR,13C NMR and mass spectroscopy. Part 5: The references: includes the list of references cited in this thesis and they are arranged according to their presence in the thesis. There are 124 references covering the period from 1961 to 2019.