Hygrocins C–G, Cytotoxic Naphthoquinone Ansamycins from <i>gdmAI</i>-Disrupted <i>Streptomyces</i> sp. LZ35

Abstract

Six hygrocins, polyketides of ansamycin class, were isolated from the <i>gdmAI</i>-disrupted Streptomyces sp. LZ35. The planar structure of hygrocins C–E (<b>1</b>–<b>3</b>) was determined by one-dimensional and two-dimensional NMR spectroscopy and high-resolution mass spectrometry. They are derivatives of hygrocin A but differ in the configuration at C-2 and the orientation of the C-3,4 double bond. Hygrocin F­(<b>4</b>) and G­(<b>5</b>) were shown to be isomers of hygrocin C (<b>1</b>) and B (<b>6</b>), respectively, due to the different alkyl oxygen participating in the macrolide ester linkage. Hygrocins C, D, and F were found to be toxic to human breast cancer MDA-MB-431 cells (IC₅₀ = 0.5, 3.0, and 3.3 μM, respectively) and prostate cancer PC3 cells (IC₅₀ = 1.9, 5.0, and 4.5 μM, respectively), while hygrocins B, E, and G were inactive