JAC Advance Access originally published online on January 22, 2007
Journal of Antimicrobial Chemotherapy 2007 59(3):451-458; doi:10.1093/jac/dkl503
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Antimicrobial activity of long-chain, water-soluble, dendritic tricarboxylato amphiphiles
1 Department of Chemistry MC 0212, Virginia Tech, Blacksburg, VA 24061, USA 2 Department of Biological Sciences MC 0406, Virginia Tech, Blacksburg, VA 24061, USA
Received 30 August 2006; returned 28 September 2006; revised 10 November 2006; accepted 13 November 2006
* Corresponding author. Tel: +1-540-231-5931; Fax: +1-540-231-9307; E-mail: jofiii{at}vt.edu
Objectives: To measure the antimicrobial activities of three series of homologous, dendritic tricarboxylato (three-headed) amphiphiles against a battery of bacteria and fungi.
Methods: Three series of homologous dendritic amphiphiles were synthesized containing C13 to C22 fatty chains. Susceptibility of Escherichia coli, Klebsiella pneumoniae, Lactobacillus plantarum, Micrococcus luteus, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Mycobacterium smegmatis, Saccharomyces cerevisiae, Candida albicans, Cryptococcus neoformans and Aspergillus niger to the amphiphiles was measured by broth microdilution and reported as the MIC.
Results: Several amphiphiles from each homologous series, designed and constructed to overcome the low solubility of saturated long-chain fatty acids, had antimicrobial activity against MRSA (MIC = 36 mg/L), C. albicans (MIC = 4.4 mg/L), S. cerevisiae (MIC = 1.1 mg/L) and M. smegmatis (MIC = 8.9 mg/L). These amphiphiles had considerably better antimicrobial activities than the corresponding saturated fatty acids. Alkyl chain length influenced the values of MIC; longer chains (C18–C22) were generally more antimicrobial, but there was no uniform pattern among the microorganisms tested.
Conclusions: As the antimicrobial activity of the amphiphiles increased with increasing chain length, it is anticipated that maximum activity was not reached with these series. Thus, the identification of the optimal chain length would provide a target compound for development of low-cost, topical microbicides and anti-infectives. Further, these series of dendritic amphiphiles with the very long chains can be used as new water-soluble probes for elucidation of membrane structure and for identification of novel targets for antimicrobial design.
Keywords: synthetic lipids , solubility , fatty acids , mycobacteria