GENOTOXICITY, ANTIFUNGAL AND ANTIBACTERIAL ACTIVITY OF NEWLY SYNTHESIZED N-(3-PHTHALIDYL)AMINES AND o-BENZOYL BENZAMIDE DERIVATIVES

摘要

A number of newly synthesized phthalidylamines and o-benzoylbenzamide derivatives were evaluated for some biological activities. Synthesis was established by condensation of 3-acetoxyphthalide 1 with morpho-line, piperidine, N,N-diisobutyl-N,N-dibenzylamines and piperazine, which afforded N-(3-phthalidyl)amines 3a-d, and 4 respectively, while with N,N-diisopropylamine, o-formyl-N,N-diisopropyl benzamide 5a is formed exclusively. On the other hand, the reaction of 3-acetoxy-3-phenylphthalide 2 with secondary amines afforded o-benzoylbenzamide derivatives 5b-c, 6 in a high yield. The structure of the reaction products was established from their spectral data. These products were screened for antifungal, antibacterial and genotoxic effect. It was found that all tested compounds have antifungal activity. Compounds 1, 2, 3d and 5b were found to be active against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. Genotoxic effects using Ames test showed that Compounds 1 and 2 have a weak base-pair substitution mutagenicity while a clear base-pair substitution mutagenic activity was shown by 3a using TA100-strain of Salmonella typhimurium. Compound 4 showed a frameshift mutgenicity while a weak oxidative mutagenic action was revealed by 6. No change on the mutagenicity of the tested chemicals was observed after using the S9 metabolic activation system.