Study the Toxicity and Anticancer Activity of Some New Derivatives of Mefenamic Acid

The new 1,3-Oxazepine derivatives (IVa-d) were manufactured from the response of N-Arylhydrazone (III) based on Mefenamic acid with various cyclic carboxylic acid anhydrides such as (succinic, maleic, phthalic, and 3- nitrophthalic) anhydride by using dry benzene under reflex via (2+5) cycloaddition reaction. These compounds 1,3-Oxazepine (IV) were obtained via a four-steps- sequence reactions in good yields. Condensation reaction of mefenamic acid with chloroacetyl chloride to give 2 -[2-chloro-N-(2,3- dimethylphenyl) acetamido] benzoic acid (I), which on amination with hydrazine hydrate in ethanol to give a corresponding acid hydrazid (II). The acid hydrazide was used as the starting materials on condensation with syringe aldehyde afforded newly N-Arylhydrazone (III) in a good yield. Finally, the later compound reacted with different type of acid anhydrides to get new derivatives of 1,3-Oxazepine. The new compounds were characterized by using FT-IR, 1H-NMR, and mass spectroscopy. In addition, the potential antibacterial activities for the certain compounds were investigated by using three species of bacteria: Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli which most of the target derivatives have exhibited a good efficacy compared with ampicillin (as antibacterial). Besides the cytotoxic effect by using various concentrations of the derivatives (IVc) and (IVd) were assessed by human breast carcinoma cells (MCF-7), which have been exhibited a high effect on the concentration of 400 μl/ml with IC50 =80.20 and IC50=82.80. A tiered approach to investigate the toxicity utilized mice to estimate its acute toxicity and the result confirmed the non-toxicity of these compounds