title: Development of cyclobutene- and cyclobutane-functionalized fatty acids with inhibitory activity against Mycobacterium tuberculosis.
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.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304 (USA).
authors.forename: Wantanee
authors.initials: W
authors.lastname: Sittiwong
authors.forename: Denise K
authors.initials: DK
authors.lastname: Zinniel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fenton
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Marshall
authors.forename: Courtney B
authors.initials: CB
authors.lastname: Story
authors.forename: Bohkyung
authors.initials: B
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
authors.forename: Raúl G
authors.initials: RG
authors.lastname: Barletta
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Dussault
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003503:Cyclobutanes / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012995:Solubility; D013696:Temperature
chemical_list: D000995:Antitubercular Agents; D003503:Cyclobutanes; D005227:Fatty Acids
keywords: cyclobutanes; cyclobutenes; fatty acids; mycobacteria; tuberculosis