Sigma receptor (σR) ligands have proven to be useful as cancer diagnostics and anticancer therapeutics and their ligands have been developed as molecular probes in oncology. Moreover, various σR ligands generate cancer cell death in vitro and in vivo. These σR ligands have exhibited promising results against numerous human and rodent cancers and are investigated under preclinical and clinical study trials, indicating a new category of drugs in cancer therapy.

Multi-target-directed ligands (MTDLs) offer new hope for the treatment of multifactorial complex diseases such as Alzheimer’s Disease (AD). Herein, we present compounds aimed at targeting the NMDA and the P2X7 receptors, which embody a different approach to AD therapy. On one hand, we are seeking to delay neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand, we also aim to reduce neuroinflammation, targeting P2X7 receptors. Although the NMDA receptor is a widely recognized therapeutic target in treating AD, the P2X7 receptor remains largely unexplored for this purpose; therefore, the dual inhibitor presented herein—which is open to further optimization—represents the first member of a new class of MTDLs.

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.

In this study, a detailed phytochemical investigation of compounds in the twigs of the mistletoe Loranthus europaeus Jacq., which belongs to the Loranthaceae family, is presented. Specimens were collected from the mistletoe L. europaeus growing on oak trees in the mainland of Greece. The alliance of oaks and mistletoes became a symbol of knowledge and strength for many centuries. Although numerous compounds of aerial tissues of other mistletoes, e.g., Viscum album, have been published, few studies have been conducted to investigate the metabolic and physiological traits of the hemiparasitic, deciduous Loranthus europaeus. LC-HRMS-based analysis led to a detailed characterization of ethyl acetate and dichloromethane extracts of the twigs of L. europaeus, which, to the best of our knowledge, exhibit enhanced antioxidant potential. Hence, twenty-four and twenty-six compounds were tentatively identified from the ethyl acetate and dichloromethane twigs’ extracts, respectively; these compounds belong to fatty acids, flavonoids, and flavonoid glycosides. Also, chlorophyll, soluble sugar, starch, and lipid contents in the twigs of L. europaeus, which have not hitherto been published, were investigated.

The genus Artemisia L. constitutes one of the largest and most widely distributed groups within the Asteraceae family, renowned for its pharmacological significance. Used in traditional medicine for over two millennia, Artemisia species have been employed to treat a broad spectrum of ailments, with modern pharmacological studies increasingly validating these traditional uses. Interest in the genus surged following the groundbreaking discovery of the antimalarial sesquiterpene lactone artemisinin from Artemisia annua L. Beyond antimalarial activity, Artemisia species exhibit diverse pharmacological effects including anti-inflammatory, antiproliferative, cytotoxic, antimicrobial, and antiviral properties, largely attributed to secondary metabolites such as sesquiterpene lactones, furofuran lignans, polyacetylenes, and methylated flavonoids. This present study covers the bioactivities of extracts, essential oils, and isolated compounds from Artemisia genus reported between 1998 and 2025. Representative compounds from the most characteristic classes of Artemisia secondary metabolites are linked to biological activities, incorporating in vitro and in vivo studies, pharmacokinetics, clinical data, and toxicity profiles, while for each compound species-specific origin is reported.

Natural products represent an important source of bioactive compounds; however, their complexity often challenges conventional discovery approaches. In this study, an ethyl acetate extract of Artemisia arborescens (Vaill.) L. was investigated prior to any isolation using an integrated statistical spectroscopy–driven dereplication strategy combining the HeteroCovariance Approach (HetCA), Statistical Total Correlation Spectroscopy (STOCSY), ¹ H NMR, and LC‐HRMS/MS. HetCA illustrated candidate features correlated with antileishmanial activity, predominantly associated with furofuran lignans. STOCSY facilitated metabolite annotation and distinction of structurally similar metabolites, enabling the identification of a novel lignan and a previously unreported compound in A. arborescens . Targeted isolation verified STOCSY‐guided annotations, while biological evaluation of the pure metabolites revealed that compounds 1 – 3 exhibit moderate activity against Leishmania promastigotes, despite originating from a crude extract exhibiting negligible antileishmanial activity under the initial screening conditions. These findings demonstrate that HetCA can reveal bioactive compounds independently of extract‐level activity and highlight its potential as a robust tool for broadening natural product drug discovery beyond conventional bioactivity‐guided approaches.