Discovery of antileishmanial compounds from Artemisia umbelliformis subsp. eriantha using HeteroCovariance Approach, HetCA

Natural product drug discovery faces important challenges related to efficient complex mixture analysis. To address this, dereplication strategies have been developed to enhance and accelerate the detection of bioactive compounds in plant extracts. Among these, statistical spectroscopy-based methods HeteroCovariance Approach (HetCA) and Statistical Total Correlation Spectroscopy (STOCSY) have been proposed. In this study, HetCA and STOCSY are applied to Artemisia umbelliformis subsp. eriantha extract, to discover antileishmanial compounds. Spectral data from appropriately generated extract fractions were statistically correlated with antileishmanial activity results. HetCA along with STOCSY revealed sets of NMR signals correlated to the activity and led to the identification of specific bioactive compounds. These components were purposefully isolated and tested against L. infantum promastigotes, designating that the positively correlated compounds 5-deoxy-5-hydroperoxytelekin 1 and telekin 2 exert strong antileishmanial effects, with a half-maximal effective concentration (EC₅₀) of 4.5 and 5.1 μΜ, respectively. Their toxicity was also tested on model host cells, THP-1 macrophages, yielding a 50 % cytotoxic concentration of 29.7 μΜ and 15 μΜ, respectively. For verification purposes, non-correlated compounds were also isolated and didn't show significant antileishmanial activity. Overall, the combination of HetCA and STOCSY was able to identify the most active compounds, facilitating the detection of bioactive components and opening new insights into natural product drug discovery.