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

• Published in: Chemistry and physics of lipids Vol. 178; pp. 84 - 91
• Main Authors: Sanabria-Ríos, David J., Rivera-Torres, Yaritza, Maldonado-Domínguez, Gamalier, Domínguez, Idializ, Ríos, Camille, Díaz, Damarith, Rodríguez, José W., Altieri-Rivera, Joanne S., Ríos-Olivares, Eddy, Cintrón, Gabriel, Montano, Nashbly, Carballeira, Néstor M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.02.2014
• Subjects: 2-Alkynoic fatty acids; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Drug Resistance, Multiple - drug effects; Fatty Acids, Unsaturated - chemical synthesis; Fatty Acids, Unsaturated - chemistry; Fatty Acids, Unsaturated - pharmacology; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Micelles; Microbial Sensitivity Tests; MRSA; Nosocomial infections; Synthesis; Synthesis; Nosocomial infections; 2-Alkynoic fatty acids; Antibacterial agents; Micelles; MRSA
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2013.12.006

•We carried out the total synthesis of four 2-AFAs and other derivatives.•We determined the antibacterial activity of 2-AFAs against MRSA.•Increasing the carbon chain length in 2-AFA, decrease its antibacterial activity.•Triple bond at C-2 and carboxylic acid moieties in antibacterial 2-AFA are needed.•Antibacterial properties of 2-AFAs are not mediated by micelle formation. 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=15.6μg/mL), Staphylococcus saprophyticus (MIC=15.5μg/mL), and Bacillus cereus (MIC=31.3μg/mL), as well as against the Gram-negative Klebsiella pneumoniae (7.8μg/mL) and Pseudomonas aeruginosa (MIC=125μg/mL). In addition, 2-HDA displayed significant antibacterial activity against methicillin-resistant S. aureus (MRSA) ATCC 43300 (MIC=15.6μg/mL) and clinical isolates of MRSA (MIC=3.9μg/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.