JAC Advance Access originally published online on July 10, 2007
Journal of Antimicrobial Chemotherapy 2007 60(3):575-581; doi:10.1093/jac/dkm244
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In vitro activity of para-guanidinoethylcalix[4]arene against susceptible and antibiotic-resistant Gram-negative and Gram-positive bacteria
Groupe d'Etude des Vecteurs Supramoléculaires du Médicament, UMR 7565, Nancy-Université—CNRS, Faculté de Pharmacie, 5 rue Albert Lebrun, BP 80403, 54001 Nancy Cedex, France
Received 24 April 2007; returned 4 June 2007; accepted 11 June 2007
* Corresponding author. Tel: +33-383-68-2336; Fax: +33-383-68-2357; E-mail: raphael.duval{at}pharma.uhp-nancy.fr
Objectives: Emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. In this study, the in vitro antibacterial activity of para-guanidinoethylcalix[4]arene was evaluated and compared with that of its constitutive monomer, para-guanidinoethylphenol. Hexamidine, a widely used antiseptic, and synthalin A, an old antidiabetic and anti-trypanosomal compound, were chosen as references.
Methods: MIC and MBC were determined for five reference strains (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and ATCC 29213, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853), as well as five antibiotic-resistant clinical isolates. Toxicity on MRC-5 and HaCaT eukaryotic cell lines was also evaluated by MTT and Neutral Red assays.
Results: No antibacterial activity was observed for para-guanidinoethylphenol (MIC 
512 mg/L) and synthalin A (MIC 64 mg/L). Conversely, para-guanidinoethylcalix[4]arene and hexamidine: (i) showed a broad antibacterial spectrum, both on Gram-positive and on Gram-negative bacteria (MIC = 4 mg/L against E. coli and 8 mg/L against S. aureus for para-guanidinoethylcalix[4]arene), to a lesser degree against E. faecalis and P. aeruginosa (MIC = 32 mg/L); (ii) were bacteriostatic (MBC 256 mg/L); and (iii) MICs and MBCs obtained for clinical isolates were similar to those obtained with reference strains. Both compounds, the monomer and the calixarene, showed no apparent cytotoxicity, whereas hexamidine and synthalin A had significant toxic effects that increased with time and concentration and in a range of 100–1000 times that for calixarene.
Conclusions: In conclusion, results confirm para-guanidinoethylcalix[4]arene as a broad-spectrum new agent or an auxiliary in antimicrobial chemotherapy.
Keywords: calixarene , antibacterial agent , IC50 , CC50 , selectivity index