Synthesis of Some N ew Thiazole Derivatives As Potential Antic ancer Agents

Research Abstract

Abstract I Synthesis of some new thiazole derivatives as potent ial anticancer agents In the search for new cytotoxic agents with improved anticancer profile, some new thiazole derivatives which bearing a free sulfonamide moiety were synthesized. All the newly synthesized target compounds were subjected to in vitro anticancer screening against human breast cancer cell line MCF - 7 .The most potent compounds, as concluded from the ir in vitro anticancer screening, were selected to be evaluated for their in vitro inh ibitory activity against carbonic anhydrase enzyme. Moreover, a molecular docking study was carried out by docking the newly synthesized compounds in the active site of the carbonic anhydrase enzyme. The thesis includes the following parts: 1. Introduction This part includes a brief literature review on cancer, chemotherapy and radiotherapy then on the reported anticancer activity of different thiazole derivatives and sulfonamide derivatives and their mechanism s of action. In addition, various methods fo r the synthesis of thiazole and thiazolodinone derivatives were discussed. 2. Aim of the present investigation: The present investigation deals with the design and the synthesis of novel thiazole derivatives bearing a sulfonamide moiety in their molecul es in order to explore the effect of combining the thiazole moiety with the biologically active sulfonamide group on the antitumor activity of the synthesized compounds. Abstract II 3. Theoretical Discussion: This part deals with the discussion of the experimental methods adopted for the synthesis of the t arget compounds , as well as the analytical methods adopted for the identification and verification of the structures of the synthesized compounds by elemental analysis and spectroscopic methods. In addition, this s ection includes schemes (1 - 4) which illustrate the synthetic pathways adopted for the preparation of the designed compounds. 4. Experimental: This part includes the detailed practical methods fo r the synthesis of twenty new compounds, one new intermediate and fourteen known intermediates that are listed below with their elemental analyses and spectral data (IR, 1 H - NMR and mass spectroscopy). Known intermediates:  2 - Chloro - N - (4 - sulfamoylphenyl) acetamide (II).  4 - ((4 - Oxo - 4,5 - dihydrothiazol - 2 - yl)amino)benzenesulfonamide (III).  4 - ((4 - Chlorothiazol - 2 - yl)amino)benzenesulfonamide (V).  2 - Benzamidoacetic acid (IXa).  2 - (4 - Chlorobenzamido)acetic acid (IXb).  4 - Benzylidene - 2 - phenyloxazol - 5(4 H ) - one (Xa).  4 - (4 - Chloro benzylidene) - 2 - phenyl oxazol - 5(4 H ) - one ( X b).  4 - [4 - (Dimethylamino)benzylidene] - 2 - phenyloxazol - 5(4 H ) - one (Xc).  4 - Benzylidene - 2 - (4 - chlorophenyl)oxazol - 5(4 H ) - one (Xd).  4 - (4 - Chlorobenzylidene) - 2 - (4 - chlorophenyl)oxazol - 5(4 H ) - one (Xe).

Research Keywords

carbonic anhydrase-thiazole