Anti mycobacterial activity of 4 '-bromo-[1,1 '-biphenyl]-4-yl 4-x-phenylmethanone derivatives, and their acute toxicity and cytotoxicity

The antimycobacterial activity of nine biphenyl methanone (BPM) derivatives against standard strains of Mycobacterium kansasii, M. avium and M. malmoe nse was determined by colorimetric assay in microplates with the dye Alamar Blue. Acute toxicity of these compounds was also analyzed by determination of CO2 concentration in a respirometric assay using Escherichia coli. The compounds showed weak antimycobacterial activity with a minimal inhibitory concentration (MIC) over 0.038 mmol l(-1) and no toxicity was found in E. c oli up to 400 mmol l(-1). No cytotoxicity was observed on V79 cells up to 0 .35 mmol l(-1) with 7 of the BPM derivatives, with two exceptions (X = SO2C H3, NO2) that showed some toxicity. The greatest antimycobacterial activity was observed with the SO2CH3 derivative and the application of Principal C omponent Analysis (PCA) showed a relationship between structure and antimyc obacterial activity of the compounds. Two descriptors, nucleophilic superde localizability of carbon atom and pi -hydrophobic constant, were necessary to describe this relationship.