4.5 Article

New verticilides, inhibitors of acyl-CoA:cholesterol acyltransferase, produced by Verticillium sp FKI-2679

Journal

JOURNAL OF ANTIBIOTICS
Volume 65, Issue 5, Pages 255-262

Publisher

JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2012.12

Keywords

acyl-CoA:cholesterol acyltransferase; cyclodepsipeptide; fungal metabolite; inhibitor; verticilide; Verticillium

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology, Japan [18390008, 20810028]
  2. Kitasato University
  3. Grants-in-Aid for Scientific Research [20810028] Funding Source: KAKEN

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Verticillium sp. FKI-2679, a soil isolate, was found to produce inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) in a cell-based assay using ACAT1- and ACAT2-expressing CHO cells. Three new compounds, verticilides A2, A3 and B1, were isolated along with a known compound, verticilide A1, from the fermentation broth of the fungus by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Structure elucidation showed that these compounds were new cyclic depsipeptide. Verticilides A1, A2, A3 and B1 showed a degree of selectivity towards ACAT2, with IC(50)s 8.5-11-fold more potent than observed against ACAT1. The Journal of Antibiotics (2012) 65, 255-262; doi:10.1038/ja.2012.12; published online 14 March 2012

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