Synthesis And Bioactive Evaluation Of 1-(4-bromophenyl)-2-(2-methl-4-nitro-1H-imidazol-1-yl) Ethanone Oxime Derivatives

Nitroimidazole derivatives are widely used in different types of drugs,which exhibit a variety of different biologically active,such as antibacterial,anticancer,antiviral,antiparasitic and anti-histamine receptors.However,due to the high toxicity and poor pharmacokinetic properties,the structural transformation of nitroimidazoles and looking for novel drugs of efficient and low toxicity have also been the focus of research in the field of international drug.Acoording to the method of chemical synthesis,compound 1-?4-bromophenyl?-2-?2-methyl-4-nitro-1H-imidazol-1-yl?ethanone was obtained by 2-methyl-4-nitroimidazole and 2,4'-dibromo-acetophenone through nucleophilic substitution reaction.Then by the reducing action of NH₂OH·HCl,1-?4-bromophenyl?-2-?2-methyl-4-nitro-1H-imidazol-1-yl?ethanone was transformed into 1-?4-bromophenyl?-2-?2-methyl-4-nitro-1H-imidazol-1-yl?ethanone oxime.Finally,22 novel 1-?4-bromophenyl?-2-?2-methyl-4-nitro-1H-imidazol-1-yl?ethanone oxime derivatives?4a-4z?were obtained by the connection of ethanone oxime and different substituents of benzoic acid,phenylacetic acid and nicotinic acid.All of the compounds were characterized by nuclear magnetic resonance spectrometer and mass spectrometry,two compounds were characterized by single crystal X-ray diffraction analysis.The antimicrobial activities above mentioned new compounds were evaluated against B.subtilis,S.aureus,E.coli and P.aeruginosa.The antibacterial results showed that the intermediate product[1-?4-bromophenyl?-2-?2-methyl-4-nitro-1H-imidazol-1-yl?ethanone oxime]displayed better antimicrobial activity relative to the compounds 4a-4z,with IC₅₀concentration range of 2.0-8.0?g/mL.In addition,the compounds of benzoic acid or niacin ring with-Cl substituent?4h,4m,4q,4r?have much better activities than the other compounds.More importantly,the resistance of compound 4h against P.aeruginosa was very prominent,with IC₅₀<12.5?g/mL,and the inhibition against P.aeruginosa reached85%at the concentration of 3?g/mL.The anticancer biological activities?MCF-7,MGC-803,HepG-2 and Hela cell lines?and toxicity on normal cells?293T?in vitro of the new compounds were tested.Then we discussed the structure-activity relationships of these new compounds.All of the compounds displayed potent inhibitory activities against the four cancer cell lines,and we can reach the conclusion that the series of compounds have the best inhibitory activities to the cell line MCG-803,with all the IC₅₀<4?g/mL.Compound 4v contains the 6-CH₃niacin substituent showed the most prominent anticancer activity.The activity precedence relations of substituents on the phenyl ring is:meta>para>ortho.In addition,compound4o which no substituent on the phenyl ring showed the lowest activity.Overall,all the anti-proliferative activities of this series of compounds can compared with the positive control?5-fluorouracil?,indicating that the novel compounds have further developed potential as broad-spectrum anti-cancer drugs.