Abstract
Selectivity of 96 semisynthetic derivatives prepared from fungal pyripyropene A, originally isolated as a potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), toward ACAT1 and ACAT2 isozymes was investigated in the cell-based assay using ACAT1- and ACAT2-expressing CHO cells. Eighteen derivatives including PR-71 (7-O-isocaproyl derivative) showed much more potent ACAT2 inhibition (IC50: 6.0 to 62 nM) than pyripyropene A (IC50: 70 nM). Among them, however, natural pyripyropene A showed the highest selectivity toward ACAT2 with a selectivity index (SI) of > 1000, followed by PR–71 (SI, 667).
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Ohshiro, T., Ohte, S., Matsuda, D. et al. Selectivity of Pyripyropene Derivatives in Inhibition toward Acyl-CoA:cholesterol Acyltransferase 2 Isozyme. J Antibiot 61, 503–508 (2008). https://doi.org/10.1038/ja.2008.67
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DOI: https://doi.org/10.1038/ja.2008.67
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