Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against mycobacterium tuberculosis

Wantanee Sittiwong, Denise K. Zinniel, Robert J. Fenton, Darrell D. Marshall, Courtney B. Story, Bohkyung Kim, Ji Young Lee, Robert Powers, Raul G Barletta, Patrick H Dussault

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Eleven fatty acid analogues incorporating four-membered carbocycles (cyclobutenes, cyclobutanes, cyclobutanones, and cyclobutanols) were investigated for the ability to inhibit the growth of Mycobacterium smegmatis (Msm) and Mycobacterium tuberculosis (Mtb). A number of the analogues displayed inhibitory activity against both mycobacterial species in minimal media. Several of the molecules displayed potent levels of inhibition against Mtb, with MIC values equal to or below those observed with the anti-tuberculosis drugs D-cycloserine and isoniazid. In contrast, two of the analogues that display the greatest activity against Mtb failed to inhibit E. coli growth under either set of conditions. Thus, the active molecules identified herein may provide the basis for the development of anti-mycobacterial agents against Mtb.

Original languageEnglish (US)
Pages (from-to)1838-1849
Number of pages12
JournalChemMedChem
Volume9
Issue number8
DOIs
StatePublished - Jan 1 2014

Fingerprint

Cyclobutanes
Mycobacterium tuberculosis
Fatty Acids
Cycloserine
Molecules
Isoniazid
Escherichia coli
Anti-Bacterial Agents
Mycobacterium smegmatis
Growth
Pharmaceutical Preparations
Tuberculosis
cyclobutanol

Keywords

  • cyclobutanes
  • cyclobutenes
  • fatty acids
  • mycobacteria
  • tuberculosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against mycobacterium tuberculosis. / Sittiwong, Wantanee; Zinniel, Denise K.; Fenton, Robert J.; Marshall, Darrell D.; Story, Courtney B.; Kim, Bohkyung; Lee, Ji Young; Powers, Robert; Barletta, Raul G; Dussault, Patrick H.

In: ChemMedChem, Vol. 9, No. 8, 01.01.2014, p. 1838-1849.

Research output: Contribution to journalArticle

Sittiwong, Wantanee ; Zinniel, Denise K. ; Fenton, Robert J. ; Marshall, Darrell D. ; Story, Courtney B. ; Kim, Bohkyung ; Lee, Ji Young ; Powers, Robert ; Barletta, Raul G ; Dussault, Patrick H. / Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against mycobacterium tuberculosis. In: ChemMedChem. 2014 ; Vol. 9, No. 8. pp. 1838-1849.
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