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2‐Methoxylated FA Display Unusual Antibacterial Activity Towards Clinical Isolates of Methicillin‐Resistant Staphylococcus aureus (CIMRSA) and Escherichia coli
Author(s) -
Carballeira Néstor M.,
Montano Nashbly,
Morales Christian,
Mooney Joseph,
Torres Xiomara,
Díaz Dakeishla,
SanabriaRios David J.
Publication year - 2017
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-017-4262-1
Subject(s) - staphylococcus aureus , escherichia coli , antibacterial activity , chemistry , dna gyrase , minimum inhibitory concentration , stereochemistry , amino acid , bacteria , nuclear chemistry , biochemistry , biology , antibiotics , genetics , gene
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 acids 1 – 4 was determined against clinical isolates of methicillin‐resistant Staphylococcus aureus (ClMRSA) and Escherichia coli . Among the series of compounds, acid 4 was the most active bactericide towards CIMRSA displaying IC 50s (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, acids 1 and 3 were the only acids that displayed antibacterial activity towards E. coli , but 1 stood out as the best candidate with an IC 50 of 21 μg/mL. The critical micelle concentrations (CMCs) of acids 1 – 4 were also determined. The C18 acids 2 and 4 displayed a five‐fold lower CMC (15–20 μg/mL) than the C16 analogs 1 and 3 (70–100 μg/mL), indicating that 4 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. Acids 1 and 4 stand out as viable candidates to be used against E. coli and CIMRSA, respectively.