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Published on: April 25, 2015
Actinopyrone D, a new downregulator of the molecular chaperone GRP78 from Streptomyces sp
Yoichi Hayakawa1, Junki Saito1, Masumi Izawa1
1Faculty of Pharmaceutical Sciences, Department of Medicinal and Life Science, Tokyo University of Science, Chiba, Japan.
Abstract:
A new downregulator of the molecular chaperone GRP78, actinopyrone D, was isolated together with a known related compound, PM050463, from Streptomyces sp. RAG92. The molecular formula of actinopyrone D was established as C25H36O4 by high-resolution FAB-MS. NMR spectroscopic analysis revealed the structure of actinopyrone D, which consists of an α-methoxy-γ-pyrone ring and a C17 side chain containing a cis olefin moiety. Actinopyrone D and PM050463 dose-dependently inhibited 2-deoxyglucose-induced luciferase expression in HT1080 human fibrosarcoma cells transfected with a luciferase reporter plasmid containing the GRP78 promoter. Actinopyrone D inhibited GRP78 protein expression and induced cell death under endoplasmic reticulum stress.
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