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.

journal_name

Lipids

journal_title

Lipids

authors

Sanabria-Ríos DJ,Morales-Guzmán C,Mooney J,Medina S,Pereles-De-León T,Rivera-Román A,Ocasio-Malavé C,Díaz D,Chorna N,Carballeira NM

doi

10.1002/lipd.12213

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

101-116

issue

2

eissn

0024-4201

issn

1558-9307

journal_volume

55

pub_type

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