Towards new antibacterial drugs.: Interest of para-guanidinoethylcalix[4]arene

We present here the results concerning the antibacterial properties evaluation of para-guanidinoethylcalix[4]arene, compared with its constitutive monomer, the para-guanidinoethylphenol, and hexamidine (Hexomedine (R)), an antiseptic from the diamidine family widely used in therapeutic, chosen as a reference in this study for its resemblance in terms of functional groups. Antibacterial activities of those three compounds were evaluated by microdilution methods, in Mueller Hinton broth, onto 5 bacterial strains: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 & ATCC 29213 and Enterococcus faecalis ATCC 29212, according to CA-SFM and CLSI (formerly NCCLS) approved standards. In parallel, the effects of these three compounds on MRC-5 eukaryotic cell viability were evaluated with MTT assay. The results obtained here confirm a lack of activity for the monomer compound (MIC >= 512 mg/l) and a real antibacterial activity for the calixarene, comparable to hexamidine. This activity is expressed, both on Gram + and Gram- bacteria (MIC = 4 mg/l for E. coli, 8 mg/l on both S. aureus strains) and at a lesser degree on E. faecalis and P. aeruginosa (MIC = 32 mg/l). Similarly, both compounds, monomer and calixarene, slightly induce any modification on MRC-5 cells viability, and this until 168 h of treatment for concentrations reaching 10(-4) mol/L while hexamidine demonstrates a significant and increasing effect during the time of experiment and this for 100 to 1000 times lower concentrations. Thus, this study tends to confirm the significance of the organization of the para-guanidinoethylphenol monomer into its cyclic calixarenic tetramer for the gain of an antibacterial activity, similar to a widely used antiseptic one. (c) 2006 Elsevier Masson SAS. Tous droits reserves.