Mass spectrometry-guided isolation of thiodiketopiperazines from 3 an EtOAc-extract of Setosphaeria rostrata culture medium and their 4 anti-skin aging effects on TNF-α-induced human dermal fibroblasts

Abstract

Using mass spectrometry (MS)-guided isolation methods, a new thiodiketopiperazine derivative (1) and exserohilone (2) 11 were isolated from an EtOAc-extract of Setosphaeria rostrata culture medium. The chemical structure of the new compound 12 was elucidated by MS and NMR spectroscopy, and the absolute configurations were established by the quantum mechanical 13 calculations of electronic circular dichroism. All isolated compounds were examined for their effects on reactive oxygen 14 species (ROS) production, matrix metalloproteinase 1 (MMP-1) secretion, and procollagen type I α1 secretion in tumor 15 necrosis factor (TNF)-α-induced human dermal fibroblasts. Compound 1 and exserohilone (2) exhibited the inhibition of 16 TNF-α-induced ROS generation and MMP-1 secretion. Additionally, compound 1 and exserohilone (2) increased the 17 procollagen type I α1 secretion. Compound 1 docked computationally into the active site of MMP-1 (？6.0 kcal/mol).