ABSTRACT
Replacement of the native promoter of theglobal regulator LaeA-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism (ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cyclopentanes/pharmacology , Fungal Proteins/genetics , Promoter Regions, Genetic/genetics , Transcription Factors/genetics , Xylariales/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/metabolism , Cyclopentanes/chemistry , Cyclopentanes/isolation & purification , Cyclopentanes/metabolism , Fungal Proteins/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , Molecular Structure , RAW 264.7 Cells , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Xylariales/genetics , Xylariales/metabolismABSTRACT
Plancyamides A (1) and B (3), plancypyrazine A (2), and plancyols A (4) and B (5), five new compounds (1-5), and three known ones (6-8), were isolated from the whole bodies of Polyphaga plancyi Bolivar. Their structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Among them, compound 3 is racemic, chiral HPLC separation afforded its respective enantiomers. The absolute configuration of 1 was assigned by computational methods. Biological evaluation of all the compounds with exception of 7 and 8 discloses that compounds 2 and 4 could inhibit JAK3 kinase with IC50 values of 12.6 and 5.0µM, respectively. In addition, compound 4 exhibit inhibitory activity towards DDR1 kinase with IC50 value of 4.87µM.