Bioactive effects of natural and novel unnatural tropolone sesquiterpenoids in a murine cell model of renal interstitial fibroblasts

Abstract

AbstractFungal specialized metabolites often exhibit a wide range of potent bioactivities, with tropolone sesquiterpenoids (TS) representing a promising family with a variety of known bioactive properties. Here, we investigated bioactive properties of the novel TS compounds 4-hydroxyxenovulene B4, 4-dehydroxy-norpycnidione5and the structurally-related compounds 4-hydroxy-norxenovulene B6, and xenovulene B3, for which no bioactive effects have been reported yet. We detected compound-specific changes in cell shapes and ramification patterns that were strongly correlated in samples treated with structurally-similar compounds and related to the tropolone moieties present on the molecule. The number of tropolone moieties per molecule had a significant influence on survival of FAIK3-5 cells, with an increased cytotoxic effect observed with the dual-substituted compounds compared to the monotropolones. Treatment with eupenifeldin2, compound4and5demonstrated versatile influences on cellular behaviour and can reduce EPO content in hypomethylated FAIK3-5 cells. Monotropolone5showed significantly reduced proliferation with low cytotoxic effects and could serve as a potential compound for further (pre-)clinical drug testing for cancer treatment. Our results bring us one step closer to linking the molecular structures of bioactive TS compounds to their biological effects and may improve their potential for clinical applications.