Mass spectrometry-guided isolation of thiodiketopiperazines from an EtOAc-extract of Setosphaeria rostrata culture medium and their anti-skin aging effects on TNF-α-induced human dermal fibroblasts

Using mass spectrometry (MS)-guided isolation methods, a new thiodiketopiperazine derivative (1) and exserohilone (2) were isolated from an EtOAc-extract of Setosphaeria rostrata culture medium. The chemical structure of the new compound was elucidated by MS and NMR spectroscopy, and the absolute configurations were established by the quantum mechanical calculations of electronic circular dichroism. All isolated compounds were examined for their effects on reactive oxygen species (ROS) production, matrix metalloproteinase 1 (MMP-1) secretion, and procollagen type I alpha 1 secretion in tumor necrosis factor (TNF)-alpha-induced human dermal fibroblasts. Compound 1 and exserohilone (2) exhibited the inhibition of TNF-alpha-induced ROS generation and MMP-1 secretion. Additionally, compound 1 and exserohilone (2) increased the procollagen type I alpha 1 secretion. Compound 1 docked computationally into the active site of MMP-1 (-6.0 kcal/mol).