Activity and Synergistic Antimicrobial Activity Between Diketopiperazines Against Bacteria In Vitro

Abstract

The aim of the present study was to determine the synergistic effects of diketopiperazines [cyclo-(L-Pro-L-Leu) (1), cyclo-(D-Pro-L-Leu) (2), and cyclo-(D-Pro-L-Tyr) (3)] purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) sp. on the growth of bacteria. The minimum inhibitory concentration and minimum bactericidal concentration of the diketopiperazines was compared with that of the standard antibiotics. The synergistic antibacterial activities of the combination of diketopiperazines against pathogenic bacteria were assessed using the checkerboard assay and time-kill methods. The results of the present study showed that the combination effects of diketopiperazines were predominately synergistic (FIC index <0.5). Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 4-12 h of treatment with 50:50 ratios of diketopiperazines. These results suggest that the combination of diketopiperazines may be microbiologically beneficial. The three diketopiperazines are nontoxic to normal human cell line (L231 lung epithelial) up to 200 m μg/ml. The in vitro synergistic activity of cyclo-(L-Pro-L-Leu), cyclo-(D-Pro-L-Leu), and cyclo-(D-Pro-L-Tyr) against bacteria is reported here for the first time. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (diketopiperazines).

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Preliminary study on synergistic combinations of raw honey with gentamicin against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa of veterinary origin

“…Antagonism results if the combination provides an effect less than the effect of either agent alone or less than the sum of the effects of the individual agents [20]. Recently, synergistic action between honey and curcuma starch was reported for E. coli and P.…”

Combination of extracts from Aristolochia cymbifera with streptomycin as a potential antibacterial drug

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