Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including Acmella bellidioides, Campuloclinium macrocephalum, Grindelia pulchella, Grindelia chiloensis, Helenium radiatum, and Viguiera tuberosa, along with pure phytochemicals isolated from Asteraceae: mikanolide (1), eupatoriopicrin (2), eupahakonenin B (3), minimolide (4), estafietin (5), 2-oxo-8-deoxyligustrin (6), santhemoidin C (7), euparin (8), jaceidin (9), nepetin (10), jaceosidin (11), eryodictiol (12), eupatorin (13), and 5-demethylsinensetin (14). Results showed that the dichloromethane extracts of C. macrocephalum and H. radiatum and the methanolic extracts prepared from C. macrocephalum and G. pulchella were highly active and selective against DENV-2, affording EC₅₀ values of 0.11, 0.15, 1.80, and 3.85 µg/mL, respectively, and SIs of 171.0, 18.8, >17.36, and 64.9, respectively. From the pool of phytochemicals tested, compounds 6, 7, and 8 stand out as the most active (EC₅₀ = 3.7, 3.1, and 6.8 µM, respectively; SI = 5.9, 6.7, and >73.4, respectively). These results demonstrate that Asteraceae species and their chemical constituents represent valuable sources of new antiviral molecules.

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects 6–7 million people worldwide. The dichloromethane extract obtained from the aerial parts of Gymnocoronis spilanthoides var subcordata showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: ent-9α,11α-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16R)-ent-11α-hydroxy-15-oxokauran-19-oic acid and ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid. These compounds showed IC₅₀ values of 10.6, 15.9 and 4.8 µM against T. cruzi epimastigotes, respectively. When tested against amastigotes, the diterpenoids afforded IC₅₀ values of 6.1, 19.5 and 60.6 µM, respectively. The cytotoxicity of the compounds was tested on mammalian cells using an MTT assay, resulting in CC₅₀s of 321.8, 23.3 and 14.8 µM, respectively. The effect of adenostemmoic acid B on T. cruzi was examined at the ultrastructural level using transmission microscopy. Treatment with 20 μM for 48 h stimulated the formation of abnormal cytosolic membranous structures in the parasite. This compound also showed an anti-inflammatory effect in murine macrophages stimulated with LPS and other TLR agonists. Treatment of macrophages with adenostemmoic acid B was able to reduce TNF secretion and nitric oxide production, while increasing IL-10 production. The combination of adenostemmoic acid B with benznidazole resulted in greater inhibition of NF-kB and a decrease in nitrite concentration. The administration of adenostemmoic acid B to mice infected with trypomastigotes of T. cruzi at the dose of 1 mg/kg/day for five days produced a significant decrease in parasitemia levels and weight loss. Treatment with the association with benznidazole increased the survival time of the animals. In view of these results, adenostemmoic acid B could be considered a promising candidate for further studies in the search for new treatments for Chagas disease.

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. An estimated 700,000 to 1 million new cases occur annually. Current therapies are limited by high toxicity, cost, prolonged treatment period, and rising resistance in endemic regions. The Asteraceae family has emerged as a promising source of bioactive compounds with proven leishmanicidal activity. In this study, the assessment of the antileishmanial activity of Helianthus tuberosus and Vernonanthura squamulosa extracts, the isolation of the sesquiterpene lactones heliangin and glaucolide A, respectively, and the evaluation of the activity of the compounds were conducted. Dichloromethane extracts of H. tuberosus and V. squamulosa were active on Leishmania amazonensis promastigotes, inhibiting the replication of the parasites in 97.2 ± 3.1% and 89.1 ± 1.1%, respectively, at 100 μg/mL. Heliangin was active against promastigotes of L. amazonensis (IC₅₀ = 9.3 μM) and intracellular amastigotes (IC₅₀ = 0.8 μM), while glaucolide A exhibited moderate activity against promastigotes (IC₅₀ = 46.7 μM) and did not show activity against intracellular amastigotes. Based on these results, heliangin was further evaluated in an animal model of cutaneous leishmaniasis using BALB/c mice infected with L. amazonensis. Heliangin (8 mg/Kg), when administered in combination with Glucantime, significantly reduced lesion progression and parasite load compared to the vehicle-treated group (p < 0.001). These findings show that heliangin is a potential candidate for leishmaniasis treatment, especially in combination with therapeutic drugs.

This study presents a comparative in vitro evaluation of 24 natural sesquiterpene γ-lactones and selected semisynthetic derivatives against three trypanosomatid parasites responsible for neglected tropical diseases: Trypanosoma brucei brucei, Trypanosoma cruzi, and Leishmania amazonensis. The compounds were screened for antiparasitic activity across different parasite life stages, and their cytotoxicity was assessed in mammalian cells. Several compounds demonstrated high inhibitory activity (>95%) at 10 µg/mL, including estafiatin (1), grossheimin (4), cynaropicrin (5), argolide (2) derivatives, and arglabin (23). However, a marked decrease in activity was observed at lower concentrations and in intracellular parasite models, particularly for T. cruzi and L. amazonensis amastigotes. Among the tested compounds, dihydroargolide (3) and pulchellin C (19) exhibited comparatively lower cytotoxicity and were further evaluated, yielding IC₅₀ values of 10.51 ± 1.72 µg/mL and 2.51 ± 1.13 µg/mL against T. b. brucei, respectively. Against L. amazonensis promastigotes, estafiatin (1), 8α-chloroacetoxygrossheimin (12), and arglabin (23) showed IC₅₀ values of 0.16 ± 0.13, 0.35 ± 0.18, and 0.58 ± 0.11 µg/mL, respectively, although their selectivity indices remained limited. Comparative analysis of the dataset indicates that specific structural elements, such as the α-methylene-γ-lactone moiety and selected substituents (e.g., epoxy and acetyl groups), may influence antiparasitic activity in a species-dependent manner. At the same time, the generally low selectivity indices and reduced activity in intracellular models highlight important limitations of these compounds as direct drug leads. Overall, this work provides a systematic comparative dataset and identifies preliminary structure–activity trends that may guide further chemical optimization of sesquiterpene γ-lactones as antiparasitic hit compounds.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, highlighting the need to identify novel bioactive compounds with antitumor potential. Natural products constitute a valuable source of molecules with anticancer activity. In this study, we performed a comparative analysis of two classes of natural compounds—sesquiterpene lactones (achillin and polymatin A) and naphthoquinones (α, β-lapachone and lapachol)—in human PDAC cell lines on cell proliferation, metabolic activity and cell death induction and early mitochondrial alterations. Achillin showed limited antiproliferative, metabolic, and cytotoxic activity, whereas polymatin A exhibited activity in the micromolar range, yielding LC₅₀ values of 16.11 ± 2.27 μM and 20.00 ± 1.90 μM for PANC-1 and MIAPaCa-2 cells, respectively. The naphtoquinones α- and β-lapachone effectively inhibited proliferation and metabolic activity and triggered cell death in both PDAC cell lines, with β-lapachone consistently displaying the highest activity with an LC₅₀ of 4.00 ± 0.07 μM for PANC-1 cells and 3.89 ± 0.50 μM for MIAPaCa-2. Interestingly, achillin, polymatin A, α- and β-lapachone selectively induced cell death while sparing PBMCs. In contrast, lapachol showed weak activity, failing to achieve 50% inhibition or cell death within the tested concentration range and lacking tumor selectivity. Mechanistically, quinone derivatives promoted early mitochondrial superoxide modulation and membrane depolarization, consistent with a redox-active profile, whereas sesquiterpene lactones induced mitochondrial depolarization with limited mitochondrial superoxide overproduction, suggesting a distinct bioenergetic disruption phenotype. Overall, these findings highlight structure–activity relationships among natural compounds and support further investigation of achillin, polymatin A and α,β-lapachone as promising molecular scaffolds in PDAC research.

The Helianthus genus comprises more than 60 species distributed throughout North and Central America, with a few extending into South America. Among these, H. annuus and H. tuberosus represent the most widely utilized and extensively investigated species. The aim of this paper is to provide an overview of the current knowledge regarding the phytochemical composition and biological activities of Helianthus species. Phytochemical studies of Helianthus taxa have demonstrated that terpenoid constituents, including sesquiterpene lactones, diterpenes, and triterpenes, together with phenolic compounds, constitute the principal classes of secondary metabolites. Pharmacological investigations on Helianthus extracts have revealed a broad spectrum of biological activities. More than twenty distinct bioactivities have been reported for H. annuus, with the majority supported by in vitro assays (≈26 reports), reflecting multiple experimental evaluations per activity using different plant parts, extracts, and models; followed by a substantial number of in vivo studies in animal models (≈21 reports), and very limited clinical evidence. In comparison, five bioactivities have been described for H. tuberosus, mainly in vitro with a few in vivo reports, whereas only single in vitro bioactivities have been described for H. salicifolius and H. angustifolius. Among these, antidiabetic, antioxidant, antimicrobial, and anticancer properties are the most frequently documented.