Antibacterial Activity of Hexadecynoic Acid Isomers toward Clinical Isolates of Multidrug‐Resistant Staphylococcus aureus

Abstract

In the present study, the structural characteristics that impart antibacterial activity to C16 alkynoic fatty acids (aFA) were further investigated. The syntheses of hexadecynoic acids (HDA) containing triple bonds at C‐3, C‐6, C‐8, C‐9, C‐10, and C‐12 were carried out in four steps and with an overall yield of 34–78%. In addition, HDA analogs containing a sulfur atom at either C‐4 or C‐5 were also prepared in 69–77% overall yields, respectively. Results from this study revealed that the triple bond at C‐2 is pivotal for the antibacterial activity displayed by 2‐HDA, while the farther the position of the triple bond from the carbonyl group, the lower its bactericidal activity against gram‐positive bacteria, including clinical isolates of methicillin‐resistant Staphylococcus aureus (CIMRSA) strains. The potential of 2‐HDA as an antibacterial agent was also assessed in five CIMRSA strains that were resistant to Ciprofloxacin (Cipro) demonstrating that 2‐HDA was the most effective treatment in inhibiting their growth when compared with either Cipro alone or equimolar combinations of Cipro and 2‐HDA. Moreover, it was proved that the inhibition of S. aureus DNA gyrase can be linked to the antibacterial activity displayed by 2‐HDA. Finally, it was determined that the ability of HDA analogs to form micelles can be linked to their decreased activity against gram‐positive bacteria, since critical micellar concentrations (CMC) between 50 and 300 μg/mL were obtained.

Dairy Processing Affects the Gut Digestion and Microecology by Changing the Structure and Composition of Milk Fat Globules

“…The mechanism of FA regulation on the gut microbiota is summarized in Table S5. According to the gene regulation, 2-hexadecynoic acid (C16:1) showed the inhibitory activity of DNA gyrase, which is responsible for DNA replication during bacterial growth . Linoleic acid (C18:2) has inhibitory activity on the binding activity of the DNA-binding protein ToxT, thereby inhibiting the activation of the key virulence genes encoding cholera toxin (CT) and toxin-coregulated pilus (TCP) .…”

“…According to the gene regulation, 2hexadecynoic acid (C16:1) showed the inhibitory activity of DNA gyrase, which is responsible for DNA replication during bacterial growth. 31 Linoleic acid (C18:2) has inhibitory activity on the binding activity of the DNA-binding protein ToxT, thereby inhibiting the activation of the key virulence genes encoding cholera toxin (CT) and toxin-coregulated pilus (TCP). 32 In addition, linoleic acid can inhibit the peptidoglycan synthesis gene in the bacterial cell wall and interact with 2hexadecanoic acid to selectively inhibit the Fabi (nutrient component synthesis protein) of pathogens.…”

Vinyl halogenated fatty acids display antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus

“…Synthetic uFAs can directly kill multi-drug resistant bacteria at very low concentrations (i.e., at micromolar and/or nanomolar levels). 6,7 Many reports address the antibacterial properties of synthetic uFA against Gram-positive bacteria. [6][7][8][9] For example, Konthikamee et al reported the antibacterial activity of 2-alkynoic FA against Gram-positive bacteria, including Staphylococcus aureus.…”

“…6,7 Many reports address the antibacterial properties of synthetic uFA against Gram-positive bacteria. [6][7][8][9] For example, Konthikamee et al reported the antibacterial activity of 2-alkynoic FA against Gram-positive bacteria, including Staphylococcus aureus. 8 In 2014, Sanabria et al performed the first study to determine the structural characteristics needed to prepare antibacterial 2alkynoic FA.…”

“…6 In another study, Sanabria et al reported that 2-HDA displayed bactericidal activity against five CIMRSA strains (MIC = 0.24-0.49 μg/mL), which were resistant to Ciprofloxacin (Cipro), indicating that 2-HDA was the most effective treatment against CIMRSA. 7 The potential of both naturally occurring and synthetic halogenated FA against Grampositive bacteria also have been reviewed. 10 Specifically, it was reported that FA containing triple bonds, double bonds, and either bromine or chlorine atoms in their chemical structures are pivotal in their biological activity against Grampositive bacteria, including S. aureus.…”