Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids

Chemistry & Biology
Hector R MorbidoniWilliam R Jacobs

Abstract

2-Hexadecynoic acid and 2-octadecynoic acid have cidal activity against Mycobacterium smegmatis and Mycobacterium bovis BCG. At subinhibitory concentrations, M. smegmatis rapidly transformed [1-(14)C]-2-hexadecynoic acid into endogenous fatty acids and elongated them into mycolic acids. Toxic concentrations of 2-hexadecynoic acid resulted in accumulation of 3-ketohexadecanoic acid, which blocked fatty acid biosynthesis, and 3-hexadecynoic acid, an inhibitor of fatty acid degradation. The combination of these two metabolites is necessary to achieve the inhibition of M. smegmatis. We conclude that 2- and 3-hexa/octadecynoic acids inhibit mycolic acid biosynthesis, fatty acid biosynthesis, and fatty acid degradation, pathways of significant importance for mycobacteria.

References

Jan 1, 1977·Annual Review of Biochemistry·K Bloch, D Vance
Aug 12, 1986·Biochemistry·C A CaJacob, P R Ortiz de Montellano
Jun 1, 1967·Journal of Biochemistry·H OkuyamaS Nojima
Aug 1, 1982·Antimicrobial Agents and Chemotherapy·J M SwensonV A Silcox
Nov 1, 1982·Antimicrobial Agents and Chemotherapy·W KonthikameeH Gershon
Nov 1, 1993·The Medical Clinics of North America·J H Kent
Jan 1, 1996·American Journal of Respiratory and Critical Care Medicine·M M ParkW N Rom
Nov 26, 1998·Progress in Lipid Research·C E BarryY Yuan
Mar 17, 2001·The Journal of Antimicrobial Chemotherapy·N M ParrishJ D Dick
Apr 24, 2002·Biochemical and Biophysical Research Communications·Olivier D AlipuiHorst Schulz
Mar 26, 2003·The Journal of Biological Chemistry·Laurent KremerGurdyal S Besra
May 14, 2003·Archives of Internal Medicine·Elizabeth L CorbettChristopher Dye
May 22, 2003·Tuberculosis·Marcos A Espinal
Oct 1, 1952·Proceedings of the Society for Experimental Biology and Medicine·B L FREEDLANDERD BALCOM
Jan 1, 1965·Proceedings of the Society for Experimental Biology and Medicine·W SEGAL
May 17, 2005·Nature Medicine·Ernesto J Muñoz-Elías, John D McKinney
Jan 26, 2012·The Journal of Biological Chemistry·Hsiang-Tsui WangMoon-shong Tang

❮ Previous
Next ❯

Citations

Jun 4, 2013·Chemistry and Physics of Lipids·Néstor M Carballeira
Dec 25, 2013·Chemistry and Physics of Lipids·David J Sanabria-RíosNéstor M Carballeira
Aug 11, 2015·Chemistry and Physics of Lipids·Catherine VilchèzeWilliam R Jacobs
Jun 24, 2008·International Journal of Antimicrobial Agents·Pedro E Almeida da SilvaMarcos A P Martins
Nov 21, 2007·Progress in Lipid Research·N M Carballeira
Jan 15, 2015·The Journal of Organic Chemistry·Christopher J SchulzeRoger G Linington
Oct 18, 2016·European Journal of Medicinal Chemistry·Diego G GhianoGuillermo R Labadie
Jan 27, 2016·PloS One·María GetinoFernando de la Cruz
Dec 28, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·María Verónica HúmpolaGeorgina Guadalupe Tonarelli
Jan 13, 2018·Frontiers in Microbiology·Xinfeng LiJin He
Sep 4, 2015·MBio·María GetinoFernando de la Cruz
Oct 4, 2019·Chemical Biology & Drug Design·Jaishree K MaliVikas N Telvekar
Jun 3, 2011·Molecular Diversity·Guillermo R LabadieHéctor R Morbidoni
Apr 30, 2008·Mycopathologia·Siyun LiuJingguo Wang
Sep 8, 2018·Bioorganic & Medicinal Chemistry·Tejosmita SenAnil Kumar Singh
Feb 13, 2007·Bioorganic & Medicinal Chemistry·Yves L Janin
Sep 22, 2010·Bioorganic & Medicinal Chemistry·Deniz TasdemirNéstor M Carballeira
Aug 31, 2012·Bioorganic & Medicinal Chemistry Letters·Néstor M CarballeiraRafael Balaña-Fouce
Apr 29, 2019··Perttu HämäläinenMaximus D. Kaos

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.