Antimycobacterial 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. 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.
De Souza
A O
AO
Instituto de Química, Biol. Chem. Lab., Universidade Estadual de Campinas, Brasil.
Santos Júnior
R R
RR
Melo
P S
PS
Alderete
J B
JB
De Conti
R
R
Haun
M
M
Sato
D N
DN
Durán
N
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D016466:CHO Cells; D004396:Coloring Agents; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*; D009499:Neutral Red; D009696:Nucleic Acids / Q000096:biosynthesis; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004396:Coloring Agents; D009696:Nucleic Acids; D013778:Tetrazolium Salts; D013844:Thiazoles; D009499:Neutral Red; C022616:thiazolyl blue