Search Results (638)

The Amaryllidaceae family is a rich source of structurally diverse alkaloids with recognized neuroactive and antiparasitic properties. This study provides the first phytochemical and biological characterization of Pyrolirion boliviense and wild Stenomesson miniatum from Bolivia. Alkaloid extracts from bulbs and leaves were analysed by GC–MS and evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and Trypanosoma cruzi inhibitory activities. Thirty-two Amaryllidaceae alkaloids were identified, with P. boliviense exhibiting greater alkaloid diversity (25 compounds) and S. miniatum a higher total alkaloid content (227.86 vs. 138.92 μg Gal/100 mg DW). P. boliviense bulb extracts showed the strongest cholinesterase inhibition (AChE IC₅₀ = 6.07 ± 0.47 μg·mL⁻¹; BuChE IC₅₀ = 30.93 ± 1.17 μg·mL⁻¹), whereas S. miniatum extracts displayed weaker AChE inhibition and no detectable BuChE activity. In anti-T. cruzi assays, bulb extracts were the most active, with S. miniatum showing an IC₅₀ of 0.90 ± 0.15 μg·mL⁻¹ (SI = 20.12) and selective anti-amastigote activity (IC₅₀ = 1.42 ± 0.66 μg·mL⁻¹; SI = 12.77). These findings identify Bolivian Andean Amaryllidaceae as promising sources of bioactive alkaloids with potential applications for Alzheimer’s disease and Chagas disease drug discovery. Full article

Mother-to-child transmission (MTCT) of infectious diseases remains a public health challenge in socially vulnerable regions with limited healthcare access. This study assessed the epidemiological situation, spatial distribution, and socioeconomic context of MTCT infections—Chagas disease (ChD), syphilis, HIV, and hepatitis B (HB)—in the Gran Chaco region (Argentina–Paraguay), 2018–2024. Epidemiological data from 2877 patients enrolled in an MTCT Plus programme were analysed, alongside socioeconomic variables and spatio-temporal cluster analysis using SaTScan software. Maternal seroprevalence of ChD was 4.1%, the highest among the infections evaluated. Syphilis prevalence was 0.8%, while no HIV or HBV infections were detected among screened pregnant women. Two statistically significant spatiotemporal clusters of maternal Trypanosoma cruzi seropositivity were identified: a household-level cluster in 2018 and a regional cluster during 2019–2021. The highest prevalence of maternal ChD seropositivity was observed in census tracts with greater socioeconomic vulnerability, although this spatial overlap was assessed descriptively. These findings highlight the effectiveness of integrated maternal–child health services in ensuring coverage, timely diagnosis, and treatment in vulnerable populations. The identified spatial patterns provide evidence to support targeted surveillance and coordinated binational public health strategies in border regions affected by persistent social inequalities. Full article

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, remains a major neglected tropical disease, with millions of people living with the infection worldwide. Current treatments are effective in the acute stage of the disease, but are poorly tolerated and show reduced efficacy in chronic infections, highlighting an urgent need for novel therapeutic strategies. A key bottleneck in early-stage drug discovery is target identification, which is traditionally dependent on costly and low-throughput experimental methods. Computational approaches offer a cost-effective and fast alternative to traditional methods. Methods: In this study, we present an integrated in silico pipeline that combines ligand-based and structure-based computational approaches to prioritize potential molecular targets for bioactive compounds against T. cruzi. The ligand-based component performed similarity searches across curated bioactivity databases containing known ligand–protein associations, and the most similar candidates were then further evaluated using a structure-based approach through pairwise structural alignment against the T. cruzi proteome from AlphaFold. Results: The pipeline was validated using eight compounds with known targets, successfully recovering the correct target in six cases. Additionally, two compounds with anti-T. cruzi activity but unknown mechanisms of action were analyzed to hypothesize their potential targets. Conclusions: Overall, the pipeline demonstrated moderate success, with limitations arising from challenges in handling novel chemotypes and poorly annotated targets. Nevertheless, its modular nature allows for an easy adaptation to other neglected tropical diseases, providing a flexible and cost-effective framework for early-stage target prioritization. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging global health concern due to population mobility. Although benznidazole and nifurtimox remain the only approved antiparasitic drugs, their limited efficacy in chronic infection, prolonged treatment regimens, frequent adverse effects, and variable activity across parasite strains highlight the need for new therapeutic strategies. In addition, the pathogenesis of chronic Chagas disease is driven not only by parasite persistence but also by immune-mediated tissue damage, particularly in chronic Chagas cardiomyopathy. In this review, we examine emerging therapeutic approaches that extend beyond conventional trypanocidal chemotherapy, with emphasis on natural products, antimicrobial peptides, and cell-based immunomodulatory strategies. Plant compounds and essential oils have shown antiparasitic activity through mechanisms including oxidative stress induction, membrane disruption, interference with sterol biosynthesis, and mitochondrial dysfunction, while some extracts also modulate host immune responses. Antimicrobial peptides display dual potential by directly damaging parasite membranes and organelles or by reshaping infection-associated inflammatory responses. In parallel, cell-based therapies such as mesenchymal stromal cells, tolerogenic dendritic cells, and bone marrow-derived cells have demonstrated promising cardioprotective and immunoregulatory effects in experimental chronic Chagas disease. Collectively, these approaches support a multitarget therapeutic framework in which parasite-directed and host-directed interventions may complement each other. Further mechanistic studies, standardization, and translational validation will be essential to advance these candidates toward clinically useful therapies for Chagas disease. Full article

Background/Objectives: American trypanosomiasis, caused by Trypanosoma cruzi, remains a major public health challenge due to the limited efficacy and adverse effects associated with current treatments. Octyl gallate (OG), a semi-synthetic derivative of gallic acid, has demonstrated promising biological activities, including antiparasitic effects. Methods: The in vitro trypanocidal activity of OG was evaluated against T. cruzi. Mechanism of action studies included the inhibition of the trypanothione reductase enzyme and flow cytometry assays to measure cell death pathways (propidium iodide uptake). Additionally, the immunomodulatory potential of the compound was investigated by assessing cytokine production and innate immune responses. Results: In this study, the trypanocidal activity of OG against different evolutionary forms of T. cruzi was investigated. Using MTT-based viability assays, OG exhibited significant activity against epimastigotes (IC50 = 5.92 ± 0.47 µM), trypomastigotes (EC50 = 3.20 ± 0.14 µM), and intracellular amastigotes (EC50 = 4.07 ± 0.72 µM). The compound also demonstrated favorable selectivity indices, particularly against trypomastigotes and amastigotes, indicating selective toxicity toward the parasite compared to mammalian host cells. In infected macrophages, OG increased TNF-α and IL-12 production while reducing IL-10 and IL-6 levels, in addition to stimulating reactive oxygen species (ROS) and nitric oxide (NO) production, suggesting an immunomodulatory effect that contributes to parasite control. Molecular docking analyses revealed a favorable interaction between OG and trypanothione reductase (TR), while biochemical assays demonstrated reduced NADPH consumption, indicating interference with TR activity. Ultrastructural analysis revealed severe morphological alterations, including membrane disruption, cytoplasmic disorganization, mitochondrial swelling, and features consistent with apoptosis-like cell death. Conclusions: Collectively, these findings demonstrate that OG exhibits potent and selective trypanocidal activity associated with immunomodulatory effects, ultrastructural damage, and disruption of parasite redox metabolism through TR inhibition, supporting its potential as a candidate for future preclinical studies against Chagas disease. Full article

Chagas disease is a parasitic infection caused by Trypanosoma cruzi and remains an important public health problem with changing epidemiological patterns. Both the acute and chronic phases pose diagnostic and prognostic challenges due to the disease’s heterogeneous clinical course. Chronic inflammation and fibrosis associated with Chagas disease lead to anatomical and morphological changes, as well as increased release of inflammatory mediators. These factors may contribute to alterations in blood viscosity and hemorheological behavior. This study aimed to evaluate hemorheological properties and inflammatory cytokine levels in individuals with chronic Chagas disease. Blood samples from 18 individuals infected with T. cruzi and 15 uninfected controls were analyzed. Rheological parameters were measured using a rheometer, and cytokine levels were quantified by flow cytometry. The infected group had a mean age of 57.25 years, including both sexes. The mean time since laboratory diagnosis was 13 years. Hematological analysis demonstrated significant alterations in leukocyte subpopulations and erythrocyte-related parameters, including lymphocyte count, red blood cell indices, hemoglobin, hematocrit, and platelet-related markers. Blood samples from both groups demonstrated non-Newtonian fluid behavior and non-linear flow curves. However, individuals infected with T. cruzi presented significant alterations in blood viscosity compared to controls. Increased serum levels of IL-1β, IL-6, CXCL8 (IL-8), and IL-10 were also observed in infected individuals. The blood viscosity showed a significant positive correlation with CXCL8 (IL-8) and IL-10 levels. These findings suggest that cytokine-associated hemorheological alterations may contribute to the pathophysiology and clinical progression of chronic Chagas disease. Full article

Euterpe oleracea Mart. (açaí), a palm fruit native to the Amazon basin, has attracted growing global scientific interest over the past decade owing to its distinctive phytochemical richness and broad functional potential. This narrative review synthesizes research published between 2015 and 2025 on açaí’s nutritional composition, biological activities, food technological applications, processing innovations, by-product valorization, and sustainability challenges. Açaí pulp contains a distinctive nutrient matrix—including anthocyanins (particularly cyanidin-3-glucoside), polyphenols, oleic and linoleic fatty acids, and dietary fiber—underpinning antioxidant, anti-inflammatory, cardioprotective, hepatoprotective, and antiobesity effects demonstrated primarily in in vitro and animal models, with human clinical evidence still limited. Processing strategies such as ultrasound-assisted extraction, nanoencapsulation, freeze-drying, and supercritical CO₂ extraction have advanced bioactive stability and bioaccessibility, enabling açaí’s incorporation into dairy products, functional beverages, biodegradable packaging, reformulated meat products, and edible films. Processing residues—seeds and pomace—are increasingly repurposed into nutraceuticals, biosorbents, and bio-based polymers, reinforcing the species’ circular bioeconomy potential. Food safety risks, particularly Trypanosoma cruzi contamination in minimally processed products, require standardized mitigation protocols. Key remaining challenges include the absence of validated bioaccessibility methodologies, the scarcity of human clinical trials, and the need for scalable processing technologies suitable for smallholder production contexts. Overall, açaí emerges as a model bioresource at the convergence of nutrition science, food technology, and environmental sustainability. Full article

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), includes clinically relevant intestinal inflammation; however, the mechanisms associated with tissue injury remain incompletely understood. ArtinM is an immunomodulatory lectin with known effects on innate and adaptive immunity, although its intestinal role during acute T. cruzi infection remains unclear. This study investigated whether ArtinM modulates the intestinal inflammatory response during acute experimental T. cruzi infection. In vivo, BALB/c mice were allocated to Saline control, T. cruzi + Saline, and T. cruzi + ArtinM groups. Intestinal inflammatory infiltrate and tissue concentrations of TNF-α, IFN-γ, IL-12p40, and IL-10 were quantified. Acute infection markedly increased TNF-α, IFN-γ, IL-12p40, and inflammatory infiltrate, whereas ArtinM significantly attenuated these responses. TNF-α, IFN-γ, and IL-12p40 remained associated with group after adjustment for infiltrate, whereas IL-10 reached statistical significance only in the adjusted model and was therefore interpreted cautiously. In parallel, an exploratory analysis of a public murine intestinal scRNA-seq dataset (GSE319934; GSM9529706 and GSM9529707), derived from a chronic infection setting, was performed to provide pathway-level context for inflammatory mediators assessed in vivo. This transcriptomic analysis indicated that related inflammatory, innate immune, chemotactic, and adhesion-associated genes were detectable in intestinal single-cell data from T. cruzi infection. However, because this dataset was not temporally matched to the acute model, it was not interpreted as a phase-matched comparator, mechanistic validation, or temporal extension of the experimental findings. Together, the results support that ArtinM treatment is associated with attenuation of acute intestinal inflammatory outcomes in experimental T. cruzi infection. Because local intestinal parasite burden was not measured, these findings should be interpreted as evidence of inflammatory modulation rather than as direct evidence of local antiparasitic activity. The public scRNA-seq analysis provides only exploratory contextual information for related inflammatory pathways. Full article

Background: Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging concern worldwide. Current chemotherapies show limited efficacy during chronic infection, and no licensed vaccine is currently available. We previously developed the chimeric antigen N-Tc52/TSKb20 as a vaccine candidate against T. cruzi infection. In a murine model, this vaccine induced robust antigen-specific immune response associated with protection shortly after vaccination. Objectives: Here, we investigated the long-term persistence and effector functions of the immune responses elicited by this vaccine candidate. Methods: Both female and male C57BL/6 mice were immunized with three doses of N-Tc52/TSKb20 formulated with QuilA adjuvant. Serum samples collected 170 days post-immunization were analyzed for antigen-specific antibodies by ELISA and for trypanolytic activity against cell-derived trypomastigotes using an in vitro functional assay. Cellular immune responses were evaluated by measuring cytokine production, T cell activation, and memory T cell responses following in vitro re-stimulation with the vaccine antigen or T. cruzi antigens. Results: N-Tc52/TSKb20 vaccination induced a sustained antigen-specific humoral response, characterized by long-lasting IgG2c antibodies and functional activity persisting for up to 170 days post-immunization. In parallel, vaccination promoted long-term activation of antigen-specific CD8⁺ T cells and production of TNF-α and IFN-γ upon antigen re-encounter. A sex-dependent tendency was observed for IL-10, with increased production in vaccinated female mice. Moreover, vaccinated animals exhibited increased frequencies of central and effector memory CD4⁺ and CD8⁺ T cells in response to T. cruzi antigens, with a predominant contribution of CD8⁺ T cells, indicating the establishment of parasite-specific T cell memory. Conclusions: Together, these findings demonstrate that vaccination with N-Tc52/TSKb20 induces a long-lasting Th1-biased immune response characterized by trypanolytic antibodies, functional and durable T cell responses, and parasite-specific memory T cells. This immunological profile supports the potential of N-Tc52/TSKb20 as a promising vaccine candidate for Chagas disease and highlights its capacity to elicit immune mechanisms that have been associated with protection against T. cruzi infection. Full article

Background/Objectives: Jatrophone is a bioactive diterpenoid with reported antitrypanosomal activity; however, its development as a lead compound is limited by pronounced cytotoxicity toward mammalian cells. This study aimed to explore the structural modification of jatrophone through triazole functionalization to modulate its antiparasitic activity and improve selectivity against Trypanosoma cruzi. Methods: A series of mono- and bis-triazole jatrophone derivatives was semi-synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) from a stereoselectively prepared diazido intermediate. Jatrophone, its azido precursor, and the synthesized triazole derivatives were evaluated in vitro against T. cruzi epimastigotes and intracellular amastigotes. Cytotoxicity toward mammalian host cells was assessed in parallel to determine selectivity indices. Results: Jatrophone exhibited potent activity against epimastigotes but showed poor selectivity due to significant mammalian cell toxicity. Introduction of azide and triazole functionalities altered the biological profile of the parent scaffold, leading to derivatives with reduced cytotoxicity and improved selectivity in extracellular assays. Among the evaluated compounds, a mono-triazole derivative bearing a methylene-linked cycloalkyl substituent retained antiparasitic activity while displaying markedly lower toxicity toward mammalian cells. However, in the intracellular amastigote model, most derivatives demonstrated a substantial reduction in selectivity, indicating limited translation of extracellular activity to the intracellular parasite stage. Conclusions: Triazole functionalization of the jatrophone scaffold represents a viable strategy to modulate its biological properties and reduce host-cell toxicity. Nevertheless, the reduced efficacy observed in intracellular assays underscores the limitations of epimastigote-based screening and highlights the challenges in developing selective intracellular antitrypanosomal agents from the jatrophone scaffold. Full article

Chagas disease and trichomoniasis are two neglected parasitic infections (NPIs) in need for new therapies that address both the toxicity and limited bioavailability impacting on the effectiveness of benznidazole (BZ) and nifurtimox, the only drugs available for treating the infection caused by Trypanosoma cruzi, as well as the resistance that Trichomonas vaginalis has developed to 5-nitroimidazoles. Herein, we report the outcomes of the primary screening of a series of eighteen quinoxaline-1,4-di-N-oxides (QdNOs) carried out against both protozoan parasites. Computational approaches revealed that these derivatives have adequate oral bioavailability and do not pose toxicity risks associated with their chemical structures. Meanwhile, biological studies disclosed that compounds 4b and 4m exhibit considerable activity against T. cruzi at the highest concentration tested, showing 4m a trypanocidal profile (IC₅₀ = 23.66 µM) similar to that of BZ (IC₅₀ = 21.66 µM), and a selectivity index (SI) > 5.32. Regarding the activity on T. vaginalis, derivative 4n stands out with an IC₅₀ value of 9.85 µM, showing no cytotoxicity towards mammalian cells. However, their potency decreases when tested over resistant parasites. Alterations in either the hydrogenosomal membrane potential or the production of reactive oxygen species (ROS) were also explored. The findings suggest that the trichomonacidal activity of compound 4n is not mediated by a direct disruption of hydrogenosomal bioenergetics or a pro-oxidant effect. Altogether, these preliminary results support that the QdNO scaffold could be introduced as a proper template for developing novel trypanocidal and trichomonacidal agents. Full article

Trypanosoma cruzi exhibits complex genetic diversity, organized into seven distinct typing units. To complete its life cycle, the parasite must adapt to the digestive tract of various species of triatomine bugs. This systematic review aimed to understand the molecular adaptation mechanisms of T. cruzi in relation to different vector species, systematizing knowledge on vector competence. Following PRISMA guidelines, 18 experimental studies (published between 1995 and 2025) were selected from the ScienceDirect, PubMed, Scopus, and Web of Science databases, focusing on the parasite–vector interface and proteomic analyses. There was a predominance of studies conducted in Brazil (66.67%), using the Rhodnius prolixus model (72.22%) and the TcI strain (clone Dm28c). The evolution of methodological approaches reflects a transition from classical techniques, such as SDS-PAGE, to high-throughput omics strategies, including LC-MS/MS and gene editing tools such as CRISPR. The findings were organized into key biological processes, including parasite adhesion mediated by perimicrovillar membrane components, glycoinositolphospholipids (GIPLs), and mucins; the influence of the metabolic and nutritional microenvironment, particularly hemoglobin-derived peptides and glucose availability; and the role of intestinal redox conditions in triggering metacyclogenesis. Overall, the available evidence suggests that T. cruzi adaptation within triatomine vectors is a multifactorial process driven by proteomic reprogramming and post-transcriptional regulation in response to environmental signals within the vector gut. However, this understanding is largely derived from studies based on Rhodnius prolixus and TcI strains, which limits the generalization of these mechanisms across other triatomine species and parasite lineages. Full article

Food deprivation induces intestinal adaptations in Triatoma pallidipennis, a hematophagous insect with intermittent feeding habits. The ability to survive long periods without food promotes the persistence of this vector in the environment and contributes to its evolutionary success. This study employed one- and two-dimensional electrophoretic techniques combined with Western blot to evaluate the abundance of α-tubulin, β-actin, and the heat shock protein HSP70. These proteins were more abundant in the anterior midgut tissue of unfed insects than in that of fed insects. As these responses were similar in females and males, the observed adaptations primarily depend on feeding status and intestinal region. These findings provide further insight into the intestinal physiology of T. pallidipennis, a vector of the flagellate parasite Trypanosoma cruzi, the causative agent of Chagas disease. Full article

A novel ocellatin-P1 isoform was isolated and purified from the skin secretion of the pepper frog Leptodactylus labyrinthicus. The crude skin secretion was fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC) using a C₈ column and the peptide was subsequently purified on a reversed-phase C₁₈ column. Ocellatin-LB3 (as this isoform was named) was chemically sequenced by Edman degradation. This peptide is a linear C-terminally amidated molecule composed of 25 amino acid residues: ¹GLLDTLKGAAKNVVGGLASKVMEKL²⁵-NH₂. Synthetic ocellatin-LB3 was active against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and inactive against Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. In addition, the peptide reduced the Trypanosoma cruzi infection in L6 cells. At 64 µM it did not reduce erythrocytes or polymorphonuclear leukocytes, but did reduce mononuclear leukocyte counts, as detected by flow cytometry. No hemolytic activity was observed in red blood cells even at 128 µM. The peptide exhibited limited antiproliferative activity against MCF-7 and HeLa tumor cells at 128 µM. Pre-incubation with the peptide appeared to enhance N-formylmethionine-leucyl-phenylalanine (fMLP)-induced migration, indicating a potential additive or synergistic effect on human neutrophils. The three-dimensional structure of ocellatin-LB3 was investigated by circular dichroism (CD) and nuclear magnetic resonance (NMR). In the presence of sodium dodecyl sulfate (SDS), the peptide adopts an α-helical structure spanning residues Leu³–Lys²⁴, which remains largely preserved even at 95 °C. NMR Hydrogen/Deuterium (H/D) exchange experiments suggest that ocellatin-LB3 adopts a preferential orientation when interacting with SDS micelles. Based on the similarity among ocellatins, and on the physicochemical and structural properties of this peptide, a possible membrane-mediated mode of action is proposed, although this remains to be experimentally validated. Full article

Chagas disease affects millions of people worldwide, including those in Latin America. The only drugs available for its treatment are benznidazole and nifurtimox. However, these drugs present high toxicity and limited efficacy. Therefore, the search for new treatments continues. In this regard, computer-assisted drug design has been implemented in scientific research for drug repurposing, allowing for reduced costs and time. Therefore, the objective of this work was to search for analogs of FDA-approved drugs with activity against Trypanosoma cruzi through ligand-based virtual screening and their biological evaluation against blood trypomastigotes. The compound TD-095 (LC₅₀ = 48.60 and 13.75 µM), a ketanserin analogue, TS-936 (LC₅₀ = 71.55 and 37.54 µM), a terfenadine analogue, and TD-831 (LC₅₀ = 75.94 and 26.17 µM), a sulfasalazine analogue, were considered as potential trans-sialidase inhibitors; TIM-967 (LC₅₀ = 69.70 and 39.69 µM) and LK-284 (LC₅₀ = 116.7 and 82.29 µM), two sulfonylurea analogues, were considered as potential triosephosphate isomerase inhibitors, showing better trypanocidal activity against NINOA and INC-5 strains, respectively, than the reference drugs. Molecular dynamics simulations predicted the stability of the compounds in complex with their respective proteins. Finally, the ADMET predictive analysis showed favorable properties for the compounds. These results support continued research into new agents against Trypanosoma cruzi, using structures of drugs already approved by the FDA. Full article