Vinyl halogenated fatty acids display antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus
Main Article Content
Abstract
Methicillin-resistant Staphylococcus aureus is a pathogen responsible for skin and wound infections, pneumonia, and bloodstream infections. Serious attention is needed because Methicillin-resistant S. aureus is also resistant to many other commonly used antibiotics. This study explores the potential of vinyl halogenated fatty acids as antibacterial agents. Specifically, the total synthesis of vinyl halogenated fatty acids was performed to investigate their antibacterial activity against clinical isolates of methicillin-resistant S. aureus. The novel synthesis of the vinyl halogenated fatty acids was carried out by treating either 2-dodecynoic acid or 2-hexadecynoic acid with an allyl halide and 5 mol% of bis(benzonitrile)palladium (II) chloride as catalyst. Our results demonstrate that vinyl halogenated fatty acids displayed significant antibacterial activity against clinical isolates of methicillin-resistant S. aureus and low cytotoxicity against eukaryotic Vero Cells. Moreover, it was demonstrated that vinyl brominated fatty acids could disrupt the S. aureus plasma membrane and inhibit the expression of the norB gene.
Article Details
How to Cite
SANABRIA-RIOS, David J. et al.
Vinyl halogenated fatty acids display antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus aureus.
Medical Research Archives, [S.l.], v. 10, n. 7, july 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2901>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i7.2901.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019; CS298822-A; Centers for Disease Control and Prevention: Atlanta, GA, 2019, 95-96.
2. Gade N.D., M.S. Q. Fluoroquinolone therapy in Staphylococcus aureus infections: Where do we stand? J Lab Physicians. 2013;5(2):109-112. DOI:https://dx.doi.org/10.4103/0974-2727.119862
3. Walker DD, David MZ, Catalano D, Daum R, Gluth MB. In vitro susceptibility of ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus to ototopical therapy. Otolaryngology. 2018;158(5):923-929. DOI:https://doi.org/10.1177/0194599818762382
4. Spetalnick BM, Powers JS. Eradication of methicillin-resistant Staphylococcus aureus colonization with ciprofloxacin. J Am Geriatr Soc. 1990;38(3):389-390. DOI:https://doi.org/10.1111/j.1532-5415.1990.tb03532.x
5. Desbois AP. Potential applications of antimicrobial fatty acids in medicine, agriculture and other industries. Recent Pat Antiinfect Drug Discov. 2012;7(2):111-122. DOI:https://doi.org/10.2174/157489112801619728
6. Sanabria-Ríos DJ, Rivera-Torres Y, Maldonado-Domínguez G, et al. Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria. Chemistry and physics of lipids. Feb 2014;178::84-91. DOI:https://doi.org/10.1016/j.chemphyslip.2013.12.006
7. Sanabria-Ríos DJ, Morales-Guzman C, Mooney J, et al. Antibacterial activity of hexadecynoic acid isomers toward clinical isolates of multidrug-resistant Staphylococcus aureus. Lipids. 2020;55(2):101-116. DOI:https://doi.org/10.1002/lipd.12213
8. Konthikamee W, Gilbertson JR, Langkamp H, Gershon H. Effect of 2-alkynoic acids on in vitro growth of bacterial and mammalian cells. Antimicrob Agents Chemother. November 1, 1982 1982;22(5):805-809. DOI:https://doi.org/10.1128/AAC.22.5.805
9. Sanabria-Rios DJ, Rivera-Torres Y, Rosario J, et al. Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria. Bioorg Med Chem Lett. 2015;25(22):5067-5071. DOI:https://doi.org/10.1016/j.bmcl.2015.10.022
10. Dembitsky VM, Srebnik M. Natural halogenated fatty acids: Their analogues and derivatives. Prog Lipid Res. 2002;41(4):315-367. DOI:https://doi.org/10.1016/S0163-7827(02)00003-6
11. Hirsh S, Carmely S, Kashman Y. Brominated unsaturated acids from the marine sponge Xestospongia sp. Tetrahedron. 1987;43(14):3257-3261. DOI:https://doi.org/10.1016/S0040-4020(01)90293-5
12. Bourguet-Kondracki ML, Rakotoarisoa MT, Martin MT, Guyot M. Bioactive bromopolyacetylenes from the marine sponge Xestospongia testudinaria. Tetrahedron Lett. 1992;33(2):225-226. DOI:https://doi.org/10.1016/0040-4039(92)88056-B
13. Latifah LA, Soekamto NH, Tahir A. New antibacterial activities of brominated C18 and C20 fatty acids isolated from marine sponge Xestospongia testudinaria against shrimp pathogenic bacteria. RASĀYAN J Chem. 2021;14(1):460-465. DOI:https://doi.org/10.31788/RJC.2021.1415999
14. Priimagi A, Cavallo G, Metrangolo P, Resnati G. The halogen bond in the design of functional supramolecular materials: Recent advances. Acc Chem Res. 2013;46(11):2686-2695. DOI:https://doi.org/10.1021/ar400103r
15. Wilcken R, Zimmermann MO, Lange A, Joerger AC, Boeckler FM. Principles and applications of halogen bonding in medicinal chemistry and chemical biology. J Med Chem 2013;56(4):1363-1388. DOI:https://doi.org/10.1021/jm3012068
16. Xu Z, Yang Z, Liu Y, et al. Halogen bond: Its role beyond drug–target binding affinity for drug discovery and development. J Chem Inf Model 2014;54(1):69-78. DOI:https://doi.org/10.1021/ci400539q
17. Hernandes ZM, Cavalcanti TSM, Moreira MDR, de Azevedo Junior FW, Leite LAC. Halogen Atoms in the Modern Medicinal Chemistry: Hints for the Drug Design. Curr Drug Targets. 2010;11(3):303-314. DOI:http://dx.doi.org/10.2174/138945010790711996
18. Molchanova N, Nielsen J, Sørensen K, et al. Halogenation as a tool to tune antimicrobial activity of peptoids. Sci Rep. 2020;10:14805. DOI:https://doi.org/10.1038/s41598-020-71771-8
19. Ibrahim JS, Adamu HM, Shakede OI. Antibacterial activity of Marula [Sclerocarya Birrea] and brominated Marula seed oil. IJISRT. 2020;5(8):1120-1124.
20. Carballeira NM, Alequín D, Lotti Diaz LM, et al. synthesis of a novel brominated vinylic fatty acid with antileishmanial activity that effectively inhibits the Leishmania topoisomerase IB enzyme mediated by halogen bond formation. Pure Appl Chem 2019;91(8):1405-1416. DOI:https://doi.org/10.1515/pac-2018-1113
21. Carballeira NM, Sanabria D, Cruz C, et al. 2,6-Hexadecadiynoic acid and 2,6-nonadecadiynoic acid: Novel synthesized acetylenic fatty acids as potent antifungal agents. Lipids. 2006;41(5):507-511.
22. Fass RJ. Ciprofloxacin. Best use of this new broad-spectrum antibiotic. Postgrad Med. Jun 1990;87(8):117-131. DOI:https://doi.org/10.1080/00325481.1990.11704677
23. Steinbuch KB, Fridman M. Mechanisms of resistance to membrane-disrupting antibiotics in Gram-positive and Gram-negative bacteria. 10.1039/C5MD00389J. Med Chem Comm. 2016;7(1):86-102. DOI:https://doi.org/10.1039/C5MD00389J
24. Kwak YG, Truong-Bolduc QC, Bin KH, et al. Association of norB overexpression and fluoroquinolone resistance in clinical isolates of Staphylococcus aureus from Korea. J Antimicrob Chemother. 2013;68(12):2766-2772. DOI:https://doi.org/10.1093/jac/dkt286
25. Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harb Perspect Biol. 2010;2(5):a000414-a000414. DOI:10.1101/cshperspect.a000414
26. Parsons JB, Yao J, Frank MW, Jackson P, Rock CO. Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus. J Bacteriol 2012;194(19):5294-5304. DOI:10.1128/jb.00743-12
27. Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol. 2005;187(7):2395-2405. https://doi.org/10.1128/JB.187.7.2395-2405.2005
2. Gade N.D., M.S. Q. Fluoroquinolone therapy in Staphylococcus aureus infections: Where do we stand? J Lab Physicians. 2013;5(2):109-112. DOI:https://dx.doi.org/10.4103/0974-2727.119862
3. Walker DD, David MZ, Catalano D, Daum R, Gluth MB. In vitro susceptibility of ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus to ototopical therapy. Otolaryngology. 2018;158(5):923-929. DOI:https://doi.org/10.1177/0194599818762382
4. Spetalnick BM, Powers JS. Eradication of methicillin-resistant Staphylococcus aureus colonization with ciprofloxacin. J Am Geriatr Soc. 1990;38(3):389-390. DOI:https://doi.org/10.1111/j.1532-5415.1990.tb03532.x
5. Desbois AP. Potential applications of antimicrobial fatty acids in medicine, agriculture and other industries. Recent Pat Antiinfect Drug Discov. 2012;7(2):111-122. DOI:https://doi.org/10.2174/157489112801619728
6. Sanabria-Ríos DJ, Rivera-Torres Y, Maldonado-Domínguez G, et al. Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria. Chemistry and physics of lipids. Feb 2014;178::84-91. DOI:https://doi.org/10.1016/j.chemphyslip.2013.12.006
7. Sanabria-Ríos DJ, Morales-Guzman C, Mooney J, et al. Antibacterial activity of hexadecynoic acid isomers toward clinical isolates of multidrug-resistant Staphylococcus aureus. Lipids. 2020;55(2):101-116. DOI:https://doi.org/10.1002/lipd.12213
8. Konthikamee W, Gilbertson JR, Langkamp H, Gershon H. Effect of 2-alkynoic acids on in vitro growth of bacterial and mammalian cells. Antimicrob Agents Chemother. November 1, 1982 1982;22(5):805-809. DOI:https://doi.org/10.1128/AAC.22.5.805
9. Sanabria-Rios DJ, Rivera-Torres Y, Rosario J, et al. Chemical conjugation of 2-hexadecynoic acid to C5-curcumin enhances its antibacterial activity against multi-drug resistant bacteria. Bioorg Med Chem Lett. 2015;25(22):5067-5071. DOI:https://doi.org/10.1016/j.bmcl.2015.10.022
10. Dembitsky VM, Srebnik M. Natural halogenated fatty acids: Their analogues and derivatives. Prog Lipid Res. 2002;41(4):315-367. DOI:https://doi.org/10.1016/S0163-7827(02)00003-6
11. Hirsh S, Carmely S, Kashman Y. Brominated unsaturated acids from the marine sponge Xestospongia sp. Tetrahedron. 1987;43(14):3257-3261. DOI:https://doi.org/10.1016/S0040-4020(01)90293-5
12. Bourguet-Kondracki ML, Rakotoarisoa MT, Martin MT, Guyot M. Bioactive bromopolyacetylenes from the marine sponge Xestospongia testudinaria. Tetrahedron Lett. 1992;33(2):225-226. DOI:https://doi.org/10.1016/0040-4039(92)88056-B
13. Latifah LA, Soekamto NH, Tahir A. New antibacterial activities of brominated C18 and C20 fatty acids isolated from marine sponge Xestospongia testudinaria against shrimp pathogenic bacteria. RASĀYAN J Chem. 2021;14(1):460-465. DOI:https://doi.org/10.31788/RJC.2021.1415999
14. Priimagi A, Cavallo G, Metrangolo P, Resnati G. The halogen bond in the design of functional supramolecular materials: Recent advances. Acc Chem Res. 2013;46(11):2686-2695. DOI:https://doi.org/10.1021/ar400103r
15. Wilcken R, Zimmermann MO, Lange A, Joerger AC, Boeckler FM. Principles and applications of halogen bonding in medicinal chemistry and chemical biology. J Med Chem 2013;56(4):1363-1388. DOI:https://doi.org/10.1021/jm3012068
16. Xu Z, Yang Z, Liu Y, et al. Halogen bond: Its role beyond drug–target binding affinity for drug discovery and development. J Chem Inf Model 2014;54(1):69-78. DOI:https://doi.org/10.1021/ci400539q
17. Hernandes ZM, Cavalcanti TSM, Moreira MDR, de Azevedo Junior FW, Leite LAC. Halogen Atoms in the Modern Medicinal Chemistry: Hints for the Drug Design. Curr Drug Targets. 2010;11(3):303-314. DOI:http://dx.doi.org/10.2174/138945010790711996
18. Molchanova N, Nielsen J, Sørensen K, et al. Halogenation as a tool to tune antimicrobial activity of peptoids. Sci Rep. 2020;10:14805. DOI:https://doi.org/10.1038/s41598-020-71771-8
19. Ibrahim JS, Adamu HM, Shakede OI. Antibacterial activity of Marula [Sclerocarya Birrea] and brominated Marula seed oil. IJISRT. 2020;5(8):1120-1124.
20. Carballeira NM, Alequín D, Lotti Diaz LM, et al. synthesis of a novel brominated vinylic fatty acid with antileishmanial activity that effectively inhibits the Leishmania topoisomerase IB enzyme mediated by halogen bond formation. Pure Appl Chem 2019;91(8):1405-1416. DOI:https://doi.org/10.1515/pac-2018-1113
21. Carballeira NM, Sanabria D, Cruz C, et al. 2,6-Hexadecadiynoic acid and 2,6-nonadecadiynoic acid: Novel synthesized acetylenic fatty acids as potent antifungal agents. Lipids. 2006;41(5):507-511.
22. Fass RJ. Ciprofloxacin. Best use of this new broad-spectrum antibiotic. Postgrad Med. Jun 1990;87(8):117-131. DOI:https://doi.org/10.1080/00325481.1990.11704677
23. Steinbuch KB, Fridman M. Mechanisms of resistance to membrane-disrupting antibiotics in Gram-positive and Gram-negative bacteria. 10.1039/C5MD00389J. Med Chem Comm. 2016;7(1):86-102. DOI:https://doi.org/10.1039/C5MD00389J
24. Kwak YG, Truong-Bolduc QC, Bin KH, et al. Association of norB overexpression and fluoroquinolone resistance in clinical isolates of Staphylococcus aureus from Korea. J Antimicrob Chemother. 2013;68(12):2766-2772. DOI:https://doi.org/10.1093/jac/dkt286
25. Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harb Perspect Biol. 2010;2(5):a000414-a000414. DOI:10.1101/cshperspect.a000414
26. Parsons JB, Yao J, Frank MW, Jackson P, Rock CO. Membrane disruption by antimicrobial fatty acids releases low-molecular-weight proteins from Staphylococcus aureus. J Bacteriol 2012;194(19):5294-5304. DOI:10.1128/jb.00743-12
27. Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol. 2005;187(7):2395-2405. https://doi.org/10.1128/JB.187.7.2395-2405.2005