2‐Methoxylated FA Display Unusual Antibacterial Activity Towards Clinical Isolates of Methicillin‐Resistant Staphylococcus aureus (CIMRSA) and Escherichia coli. Issue 6 (18th May 2017)

• Record Type: Journal Article
• Authors: Carballeira, Néstor M.; Montano, Nashbly; Morales, Christian; Mooney, Joseph; Torres, Xiomara; Díaz, Dakeishla; Sanabria‐Rios, David J.
• Is Part Of: Lipids. Volume 52:Issue 6(2017)
• Page Start: 535
• Page End: 548
• Publication Date: 2017-05-18
• Subjects: Antibacterial -- Escherichia coli -- Methicillin‐resistant -- Methoxylated fatty acids -- Staphylococcus aureus -- Synthesis; Lipids -- Periodicals; Lipids -- Periodicals; Lipiden; Lipides -- Périodiques; 547.77
• DOI: 10.1007/s11745-017-4262-1
• Languages: English
• ISSNs: 0024-4201

Abstract

Abstract: The naturally occurring (6 Z )‐(±)‐2‐methoxy‐6‐hexadecenoic acid (1 ) and (6 Z )‐(±)‐2‐methoxy‐6‐octadecenoic acid (2 ) were synthesized in 7–8 steps with 38 and 13% overall yields, respectively, by using an acetylide coupling approach, which made it possible to obtain a 100% cis ‐stereochemistry for the double bonds. In a similar fashion, the acetylenic analogs (±)‐2‐methoxy‐6‐hexadecynoic acid (3 ) and (±)‐2‐methoxy‐6‐octadecynoic acid (4 ) were also synthesized in 6–7 steps with 48 and 16% overall yields, respectively. The antibacterial activity of acids1 –4 was determined against clinical isolates of methicillin‐resistant Staphylococcus aureus (ClMRSA) and Escherichia coli . Among the series of compounds, acid4 was the most active bactericide towards CIMRSA displaying IC50s (half maximal inhibitory concentrations) between 17 and 37 μg/mL, in sharp contrast to the 6‐octadecynoic acid, which was not bactericidal at all. On the other hand, acids1 and3 were the only acids that displayed antibacterial activity towards E. coli, but1 stood out as the best candidate with an IC50 of 21 μg/mL. The critical micelle concentrations (CMCs) of acids1 –4 were also determined. The C18 acids2 and4 displayed a five‐fold lower CMC (15–20 μg/mL) than the C16 analogs1 and3 (70–100 μg/mL), indicating that4 exerts its antibacterial activity in a micellar state. None of the studied acids were inhibitory towards S. aureus DNA gyrase discounting this type of enzyme inhibition as a possible antibacterial mechanism. It was concluded that the combination of α‐methoxylation and C‐6 unsaturation increases the bactericidal activity of the C16 and C18 FA towards the studied bacterial strains. Acids1 and4 stand out as viable candidates to be used against E. coli and CIMRSA, respectively.