Inhibition of human topoisomerases I and II and protein tyrosine phosphatase 1B by longchain compounds from lichens

Lichens produce a diverse array of metabolites, many of which have promising bioactivities but yet remain underexplored. Among others, metabolites comprising side chains of increased length seem to be associated with noticeable bioactivities [ 1 ]. Within this study, metabolite profiling of five lichen species was conducted and seven long-chain lichen-derived metabolites – five depsides (glomellic acid, glomelliferic acid, divaricatic acid, stenosporic acid, and perlatolic acid), one depsidone (α-collatolic acid), and one diphenylether (β-collatolic acid) – were isolated using chromatographic methods. Aiming to identify new inhibitor scaffolds and to understand the impact of the length and functionalization of the side chains, they were investigated on their potential to inhibit human DNA topoisomerases I and II (hTopo I and II), therapeutic targets of anticancer agents, and protein tyrosine phosphatase 1B (PTP1B), a target whose inhibition is expected to be beneficial in the treatment of diabetes mellitus, in cell-free assays. The results demonstrated that, except for glomellic acid, all tested compounds effectively inhibited hTopo I and II. Similarly, these metabolites displayed significant inhibitory effects against PTP1B, with IC 50 values ranging from 4.01 to 19.7 μM. Molecular docking studies confirmed these results. These findings highlight the considerable potential of long-chain lichen metabolites and underline that the structural diversity of lichen compounds represents a valuable resource for developing novel bioactive molecules. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany