α-Pyrone Derivatives from a Streptomyces Strain Resensitize Tamoxifen Resistance in Breast Cancer Cells

ABSTRACT: Tamoxifen resistance (TamR) is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen. In order to look for noncytotoxic natural products with the ability to reverse TamR, an extract from strain Streptomyces sp. KIB-H0495 was detected to be active. Subsequent large scale fermentation and isolation led to the isolation of four α-pyrone derivatives including two new compounds, violapyrones J (2) and K (3), and two known analogues, violapyrones B (1) and I (4). Further bioactivity assays indicated that only 1 and 3 exerted potent resensitization effects on MCF-7/TamR cells at a concentration of 1 μM. Owing to the simple structures of 1 and 3, these two compounds might have potential for further investigation as novel tamoxifen resensitization agent in breast cancer chemotherapy. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13659-017-0136-8) contains supplementary material, which is available to authorized users.