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Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived β-lactone.

ABSTRACT: Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.

SUBMITTER: Lajkiewicz NJ

PROVIDER: S-EPMC3978386 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived β-lactone.

Lajkiewicz Neil J NJ Cognetta Armand B AB Niphakis Micah J MJ Cravatt Benjamin F BF Porco John A JA

Journal of the American Chemical Society 20140204 6

Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzy ...[more]

PMID: 24447064

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