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. 2014 Feb:178:84-91.
doi: 10.1016/j.chemphyslip.2013.12.006. Epub 2013 Dec 21.

Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria

David J Sanabria-Ríos  1 , Yaritza Rivera-Torres  2 , Gamalier Maldonado-Domínguez  2 , Idializ Domínguez  2 , Camille Ríos  2 , Damarith Díaz  2 , José W Rodríguez  3 , Joanne S Altieri-Rivera  3 , Eddy Ríos-Olivares  3 , Gabriel Cintrón  4 , Nashbly Montano  4 , Néstor M Carballeira  4
Affiliations

Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria

David J Sanabria-Ríos et al. Chem Phys Lipids. 2014 Feb.

Abstract

The first study aimed at determining the structural characteristics needed to prepare antibacterial 2-alkynoic fatty acids (2-AFAs) was accomplished by synthesizing several 2-AFAs and other analogs in 18-76% overall yields. Among all the compounds tested, the 2-hexadecynoic acid (2-HDA) displayed the best overall antibacterial activity against Gram-positive Staphylococcus aureus (MIC=15.6 μg/mL), Staphylococcus saprophyticus (MIC=15.5 μg/mL), and Bacillus cereus (MIC=31.3 μg/mL), as well as against the Gram-negative Klebsiella pneumoniae (7.8 μg/mL) and Pseudomonas aeruginosa (MIC=125 μg/mL). In addition, 2-HDA displayed significant antibacterial activity against methicillin-resistant S. aureus (MRSA) ATCC 43300 (MIC=15.6 μg/mL) and clinical isolates of MRSA (MIC=3.9 μg/mL). No direct relationship was found between the antibacterial activity of 2-AFAs and their critical micelle concentration (CMC) suggesting that the antibacterial properties of these fatty acids are not mediated by micelle formation. It was demonstrated that the presence of a triple bond at C-2 and the carboxylic acid moiety in 2-AFAs are important for their antibacterial activity. 2-HDA has the potential to be further evaluated for use in antibacterial formulations.

Keywords: 2-Alkynoic fatty acids; Antibacterial agents; MRSA; Micelles; Nosocomial infections; Synthesis.

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Figures

Figure 1
Figure 1
Wavelength of maximum absorption of rhodamine 6G with increasing concentrations of 2-AFAs in 1X PBS at 25°C. a) Monounsaturated alkynoic fatty acids; b) Diunsaturated alkynoic fatty acids. Values are reported as means ± SEM (N = 3[DS12]).
Scheme 1
Scheme 1
Total synthesis of 2-HDA, 2-ODA, and 2-ICA. i) n-BuLi, THF, -78°C, carbon dioxide(CO2), NH4Cl.
Scheme 2
Scheme 2
Total synthesis of 2,6-HDA and 2,9-HDA. i) n-BuLi, THF, -78°C, HMPA, 24 h; ii) n-BuLi, THF, -78°C, carbon dioxide (CO2), NH4Cl.
Scheme 3
Scheme 3
Total synthesis of 2-HDOH and 2-ODOH. i) n-BuLi, THF, -78°C, HMPA, 24 h; ii) PTSA, MeOH, 45°C, 24h.
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