RESUMO
The antimycobacterial activity of nine biphenyl methanone (BPM) derivatives against standard strains of Mycobacterium kansasii, M. avium and M. malmoense 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. coli 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 = SO2CH3, NO2) that showed some toxicity. The greatest antimycobacterial activity was observed with the SO2CH3 derivative and the application of Principal Component Analysis (PCA) showed a relationship between structure and antimycobacterial activity of the compounds. Two descriptors, nucleophilic superdelocalizability of carbon atom and pi-hydrophobic constant, were necessary to describe this relationship.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/farmacologia , Mycobacterium/efeitos dos fármacos , Animais , Antibacterianos/toxicidade , Antineoplásicos/toxicidade , Compostos de Bifenilo/toxicidade , Células CHO , Corantes , Cricetinae , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Vermelho Neutro , Ácidos Nucleicos/biossíntese , Sais de Tetrazólio , Tiazóis , Células Tumorais CultivadasRESUMO
The trypanocidal activity of several 3-(4'-bromo-[1,1-biphenyl]-4-yl) -3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine derivatives of the three evolutionary stages of Trypanosoma cruzi, namely the bloodstream trypomastigote form and both the proliferative epimastigote and amastigote forms, were studied. For both proliferative forms of T. cruzi, total lysis occurred at 10-60 microM for trypomastigotes at 40-200 muM. The following order of susceptibility was established: amastigotes > epimastigotes > trypomastigotes. The most were the bromo (X = g) and unsubstituted (X = b) compounds, which had 13- and 8-fold higher activity against trypomastigotes, respectively, than nifurtimox. Cytotoxicity in the Chinese hamster V-79 cell line, measured as inhibition of cell proliferation showed that all the compounds had the same range of IC50 (7.0-12.4 muM). The halogen (X = a,g,h) and the unsubstituted derivatives (X = b) were the least toxic in the series together with the compound (X = f).