Applying heterocovariance approach to discover antileishmanial compounds from Artemisia umbelliformis subsp. eriantha

Metabolomics approaches have a major contribution in the study of natural products as they offer a combination of spectroscopic techniques and multivariate statistical methods, that significantly accelerate the analysis of a complex plant extract. In this study, recently developed Heterocovariance approach (HetCA) [ 1 ] along with Statistical Total Correlation Spectroscopy (STOCSY) are applied on Artemisia umbelliformis subsp. eriantha extract, in order to facilitate the detection of antileishmanial compounds. The extract was fractionated by Centrifugal Partition Chromatography (CPC), creating fractions that reflected fluctuation in the concentration of the different components. The 1H-NMR data of the fractions were recorded, as well as their bioactivity results against Leishmania infantum promastigotes. Spectral data were then statistically correlated with antileishmanial activity results by HetCA. HetCA along with STOCSY indicated sets of NMR signals correlated to the activity, that corresponded to specific compounds. Additionally, HetCA indicated sets of NMR peaks that showed non-correlation with the bioactivity. Both correlated and non-correlated compounds were isolated purposefully and were tested against L. infantum promastigotes, showing that the positively correlated compounds 5-deoxy-5-hydroperoxy-telekin (1) and telekin (2) have potent antileishmanial activity, while the non-correlated compounds didn’t show any intense activity. The less toxic compound 1, was further evaluated against L. infantum intracellular amastigotes, resulting in an EC50 of 2.6 μΜ, indicating its potential as a promising antileishmanial agent. Overall, the combination of HetCA and STOCSY was able to identify the most active compounds, as demonstrated in this study, facilitating the discovery of bioactive components. Acknowledgements This work was supported by “GreenCosmIn” project (HORIZON-MSCA-2022-SE-01, Project code: 101131346) Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany