| Autor: |
Carballeira NM; Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, PO Box 23346, 00931-3346, San Juan, PR, USA. nestor.carballeira1@upr.edu., Montano N; Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, PO Box 23346, 00931-3346, San Juan, PR, USA., Morales C; Department of Chemistry, University of Puerto Rico, Rio Piedras Campus, PO Box 23346, 00931-3346, San Juan, PR, USA., Mooney J; Faculty of Science and Technology, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, 00919, San Juan, PR, USA., Torres X; Faculty of Science and Technology, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, 00919, San Juan, PR, USA., Díaz D; Faculty of Science and Technology, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, 00919, San Juan, PR, USA., Sanabria-Rios DJ; Faculty of Science and Technology, Inter American University of Puerto Rico, Metropolitan Campus, PO Box 191293, 00919, San Juan, PR, USA. |
| Abstrakt: |
The naturally occurring (6Z)-(±)-2-methoxy-6-hexadecenoic acid (1) and (6Z)-(±)-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. |
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