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

The new ۱,۳-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 ۳-nitrophthalic) anhydride by using dry benzene under reflex via (۲+۵) cycloaddition reaction. These compounds ۱,۳-Oxazepine (IV) were obtained via a four-steps- sequence reactions in good yields. Condensation reaction of mefenamic acid with chloroacetyl chloride to give ۲ -[۲-chloro-N-(۲,۳-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 ۱,۳-Oxazepine. The new compounds were characterized by using FT-IR, ۱H-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-۷), which have been exhibited a high effect on the concentration of ۴۰۰ μl/ml with IC۵۰ =۸۰.۲۰ and IC۵۰=۸۲.۸۰. A tiered approach to investigate the toxicity utilized mice to estimate its acute toxicity and the result confirmed the non-toxicity of these compounds.