We report here the antibacterial and antifungal activity of 8 newly synthesized and physico-chemically characterised thioureides of 2-(4-chlorophenoxy)-benzoic acid. The new compounds were prepared in three stage. Firstly, the 2-(4-chlorophenoxymethyl)-benzoic acid was prepared by treating the phtalide with p-chlorophenol potassium salt in xylene. The second stage was the synthesis of 2-(4- chlorophenoxymethyl)-benzoyl chloride by treating the corresponding acid with thionyl chloride using anhydrous 1,2-dichloroethane as solvent, followed in the third stage, by the treatment of the abovementioned chloride with ammonium thiocyanate. The 2-(4-chlorophenoxymethyl)-benzoyl isothiocyanate resulted after refluxing the reaction mixture in dry acetone. The new compounds were prepared by refluxing the isothiocyanate with primary aromatic amines in dry acetone. The obtained compounds have been characterized by their physical properties and their chemical structures were confirmed using the spectral analysis. The aim of this study was also to evaluate the in vitro antimicrobial activity of the new compounds. The in vitro antimicrobial testing was performed by binary microdilution method, in 96 multiwell plates, in order to establish the minimal inhibitory concentration (MIC), against Gram-positive (Listeria (L.) monocytogenes, Staphylococcus (S.) aureus, Bacillus (B.) subtilis), Gram-negative (Psedomonas (P.) aeruginosa, Escherichia (E.) coli, Salmonella (S.) enteritidis), as well as Candida sp., using both reference and clinical, multidrug resistant strains. Our results showed that the tested compounds exhibited a specific antimicrobial activity, depending on the nature of the substituents and their position on the benzene ring, both concerning the microbial spectrum and the MIC value. The MICs values widely ranged between 1024 mcg/ml and 32 mcg/ml. The most active proved to be N-[2-(4-chlorophenoxymethyl)-benzoyl]-N'-(2,6- dichloro-phenyl)-thiourea and N-[2-(4-chlorophenoxymethyl)-benzoyl]-N'-(4-bromo-phenyl)-thiourea, showing a large spectrum of antimicrobial activity against enterobacterial strains (E. coli and S. enteritidis), L. monocytogenes, S. aureus and Candida sp. All the tested compounds were highly active against S. aureus (MIC = 32 mcg/ml). Four of the tested compounds exhibited antifungal activity (MIC = 256-32 mcg/ml), and P. aeruginosa as well as B. subtilis were resistant to all tested compounds.
Full conference title:
16th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 16th (2006)