Synthesis, Characterization and Antimicrobial Activity Evaluation of Some New Derivatives of 6,11-dihydrodibenzo[b,e]thiepin 5,5-dioxide

摘要

The aim of the present study was the synthesis, physico-chemical characterization and in vitro antimicrobial activity evaluation of some new derivatives of 6,11-dihydrodibenzo[b,e]thiepine-5,5-dioxide. The synthesis of the new compounds was performed in several stages. Thus, by reaction of phtalide with thiophenol potassium salt, we obtained the 2-(phenylthiomethyl)benzoic acid. The acid was cyclized with polyphosphoric acid to the desired 6,11-dihydrodibenzo[b,e]thiepin-11 (6H)-one, converted afterwards to the corresponding 5,5-dioxide and subsequently to the corresponding oxime, 11-hydroxyimino-6,1 l-dihydrodibenzo[b,e]thiepin 5,5-dioxide. The acylation of this oxime with various acid chlorides afforded the new derivatives of 6,11-dihydrodibenzo[b,e]thiepin 5,5-dioxide. The new compounds were characterized by their physico-chemical properties and their chemical structures and purity were confirmed by elemental analysis and spectral analysis (1R, ~1H-NMR, ~(13)C-NMR). The original compounds were screened for their in vitro antibacterial activity against Gram -positive strains, Gram -negative bacteria and fungal strains, using both reference and clinical, multidrug resistant strains. The qualitative screening of the susceptibility spectra of various microbial strains to these compounds was performed by three adaptated diffusion methods: paper filter disk impregnation with tested substances solutions, the disposal of tested solutions in agar wells and the spotting of the tested solutions on solid medium seeded with microbial inoculums. The quantitative assay of the antimicrobial activity was performed by nutrient broth microdilution method in order to establish the minimal inhibitory concentration (MIC). The new sulfones exhibited a significant antimicrobial activity with MICs ranging from 15.6 μg/mL to 250 μg/mL.