Novel amphiphilic cyclobutene and cyclobutane cis-C18 fatty acid derivatives inhibit Mycobacterium avium subsp. paratuberculosis growth

Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin T. Sakallioglu, Robert Powers, Patrick H. Dussault, Raúl G. Barletta

Research output: Contribution to journalArticle

Abstract

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of Johne's disease in ruminants and has been associated with Crohn's disease in humans. An effective control of Map by either vaccines or chemoprophylaxis is a paramount need for veterinary and possibly human medicine. Given the importance of fatty acids in the biosynthesis of mycolic acids and the mycobacterial cell wall, we tested novel amphiphilic C10 and C18 cyclobutene and cyclobutane fatty acid derivatives for Map inhibition. Microdilution minimal inhibitory concentrations (MIC) with 5 or 7 week endpoints were measured in Middlebrook 7H9 base broth media. We compared the Map MIC results with those obtained previously with Mycobacterium tuberculosis and Mycobacterium smegmatis. Several of the C18 compounds showed moderate efficacy (MICs 392 to 824 μM) against Map, while a higher level of inhibition (MICs 6 to 82 μM) was observed for M. tuberculosis for select analogs from both the C10 and C18 groups. For most of these analogs tested in M. smegmatis, their efficacy decreased in the presence of bovine or human serum albumin. Compound 5 (OA-CB, 1-(octanoic acid-8-yl)-2-octylcyclobutene) was identified as the best chemical lead against Map, which suggests derivatives with better pharmacodynamics may be of interest for evaluation in animal models.

Original languageEnglish (US)
Article number46
JournalVeterinary Sciences
Volume6
Issue number2
DOIs
StatePublished - Jun 1 2019

Fingerprint

Cyclobutanes
Mycobacterium avium subsp. paratuberculosis
Paratuberculosis
Mycobacterium avium
paratuberculosis
Fatty Acids
fatty acids
Growth
Mycobacterium smegmatis
Mycobacterium tuberculosis
Mycolic Acids
Chemoprevention
Ruminants
octanoic acid
chemoprevention
Crohn disease
Serum Albumin
Crohn Disease
Cell Wall
pharmacology

Keywords

  • Cyclobutane derivatives
  • Cyclobutene derivatives
  • Growth inhibition
  • Mycobacterium avium subsp. paratuberculosis
  • cis-C fatty acids

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Novel amphiphilic cyclobutene and cyclobutane cis-C18 fatty acid derivatives inhibit Mycobacterium avium subsp. paratuberculosis growth. / Zinniel, Denise K.; Sittiwong, Wantanee; Marshall, Darrell D.; Rathnaiah, Govardhan; Sakallioglu, Isin T.; Powers, Robert; Dussault, Patrick H.; Barletta, Raúl G.

In: Veterinary Sciences, Vol. 6, No. 2, 46, 01.06.2019.

Research output: Contribution to journalArticle

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