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Australian Journal of Chemistry Australian Journal of Chemistry Society
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In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

Maria Ngu-Schwemlein A C , Jenna Dumond A , Lisa Rudd A B and Jean-Herbert Rigaud A
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, Winston-Salem State University, Winston-Salem, NC 27110, USA.

B Current address: Pharmacore®, GMP Analytical Chemistry, High Point, NC 27265, USA.

C Corresponding author. Email: Schwemleinmn@wssu.edu

Australian Journal of Chemistry 68(2) 218-223 https://doi.org/10.1071/CH14427
Submitted: 1 July 2014  Accepted: 1 August 2014   Published: 8 October 2014

Abstract

The antimicrobial activities of some cationic amphipathic cyclooctapeptides in combination with select antibiotics are investigated. Accordingly, cyclooctapeptides (CPs 111) derived from the sequence cyclo[Leu-d-Leu-Leu-d-Leu-Lys-d-Lys-Lys-d-Lys] were tested against Escherichia coli and Staphylococcus aureus. Synergistic effects were evaluated in combination with tetracycline, chloramphenicol, oflaxacin, rifampicin, colistin, clindamycin, and vancomycin by the checkerboard titration assay. The results show that these cyclooctapeptides are fast acting bactericidals and are comparable to the related α-helical peptides in their activities. Significantly, some of these cyclooctapeptides exert selective synergistic effects in combination with the bacteriostatic tetracycline against S. aureus; a greater than 4-fold decrease in the minimum inhibition concentration was observed. Their synergism with the other evaluated antibiotics was generally partial or additive. Cationic amphipathic cyclooctapeptides in combination with some antibiotics could offer a possible solution to the increasing antimicrobial resistance predicament.


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