Abstract
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 IC50s 8.5–11-fold more potent than observed against ACAT1.
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Acknowledgements
We are grateful to Dr LL Rudel (Wake Forest University, Winston Salem, NC, USA) for kindly providing ACAT1-CHO and ACAT2-CHO cells, Dr M Iwatsuki (Kitasato Institute for Life Sciences) for excellent assistance, Ms N Sato for measuring NMR experiments, and Ms A Nakagawa for measuring mass spectra. This work was supported by a grant-in-aid for Scientific Research (B) 18390008 (to HT) and Young Scientists (start-up) 20810028 (to DM) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by the Kitasato University Research Grant for Young Researchers (to DM).
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Ohshiro, T., Matsuda, D., Kazuhiro, T. et al. New verticilides, inhibitors of acyl-CoA:cholesterol acyltransferase, produced by Verticillium sp. FKI-2679. J Antibiot 65, 255–262 (2012). https://doi.org/10.1038/ja.2012.12
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DOI: https://doi.org/10.1038/ja.2012.12
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