Search Results (85)

Blastocystis, a common intestinal protozoan in humans, is associated with gastrointestinal disorders, irritable bowel syndrome, urticaria, and colorectal cancer. Its genetic diversity and potential for treatment resistance make it a focus of ongoing research. This study evaluated the in vitro antiprotozoal activity of a postbiotic derived from Pediococcus acidilactici as a natural alternative treatment. P. acidilactici cultures were grown in MRS broth under anaerobic conditions, and the postbiotic was collected and characterized for pH, yield, organic acid composition, and phenolic compound content. Human isolates of Blastocystis subtypes ST1 and ST3 were cultured in Jones’ medium and exposed to varying postbiotic concentrations for 72 h. Viability was assessed microscopically. The cytotoxic effect of the postbiotic-derived P. acidilactici was evaluated by investigating its impact on the viability of HT-29 cells using the Cell Counting Kit 8. The postbiotic showed a 7% yield and a pH of 4.52 ± 0.11. It contained seven different organic acids, predominantly lactic acid, and eleven phenolic compounds, with naringin as the most abundant. At 4.38 mg/mL, the postbiotic achieved over 94% inhibition and 100% inhibition at 8.75 mg/mL and above. A pH analysis confirmed that the inhibition was independent of the culture medium acidity. Cell viability was not affected at the postbiotic concentration showing 100% antiprotozoal activity (8.75 mg/mL). These findings suggest that the P. acidilactici postbiotic is effective on a mixed culture of ST1 and ST3 subtypes and holds promise as a safe, natural antiprotozoal agent. Further in vivo studies are needed to confirm this. Full article

Benzimidazole derivatives are well known for their anthelmintic activity. Investigating the potential efficacy of new derivatives of this class against various parasites is essential to identify novel drug candidates. For this purpose, an in-house molecular database was screened, and four benzimidazole-based molecules were chosen to evaluate antiprotozoal activity. The compounds (K1–K4) had been previously synthesized through a four-step procedure. The potential in vitro cytotoxic properties of the compounds were assessed against the Leishmania (L.) major strain and L929 mouse fibroblast cells. The tests indicated that K1 (3-Cl phenyl) demonstrated an antileishmanial effect (IC₅₀ = 0.6787 µg/mL) and cytotoxicity at elevated concentrations (CC₅₀ = 250 µg/mL) in healthy cells. These findings were comparable to those of AmpB. The antileishmanial activity values were determined as follows: K2; 8.89 µg/mL, K3; 45.11 µg/mL, K4; and 69.19 µg/mL. The CC₅₀ values were determined as follows: K2, 63 µg/mL; K3; 0.56 µg/mL; and K4, 292 µg/mL. Molecular docking and dynamic simulations were conducted to elucidate the potential mechanisms of action of the test substances. In silico investigations indicated interactions between the compounds and the active site of pteridine reductase 1 (PTR1), which is a biosynthetic enzyme essential for parasite proliferation. N-alkyl benzimidazole-based compounds exhibit potential inhibitory activity against L. (L.) major promastigotes. Therefore, these findings suggest that in vivo evaluation is warranted, and structural modifications may lead to the identification of more effective antileishmanial agents. Full article

The aim of this study was to evaluate bioactive properties of Basidiomycota fungi, mainly Suillus sp. Wide spectrum of activities were revealed for S. variegatus, S. luteus, S. bovinus and S. granulatus; and obtained results were compared with other common fungi. Total Phenolic Content (TPC) varied from 245.32 ± 5.45 to 580.77 ± 13.10 (mg (GAE) per 100 g of dry weight) in methanolic extracts of S. bovinus and S. granulatus fruiting bodies, respectively. In ethyl acetate extracts, the highest TPC were obtained for S. variegatus (310 ± 9.68, mg (GAE)/100 g, dry matter), and the lowest means for S. luteus (105 ± 3.55, mg (GAE)/100 g dry weight). The ethyl acetate extracts of the tested Suillus species exhibited a stronger antioxidant activity (AA) to scavenge DPPH^● and ABTS^•+ than the methanolic ones, and the highest effects were determined for S. luteus (EC₅₀, 0.15 ± 0.05 and 0.23 ± 0.05%, respectively). In the case of methanolic extracts, the highest AA were evaluated for S. granulatus. (EC₅₀ for DPPH^● and ABTS^•+, 0.81 ± 0.30 and 0.95 ± 0.22%, respectively). The ABTS^•+ scavenging potential varied from 0.25 ± 0.05 to 0.74 ± 0.10 (mmol/L, TROLOX equivalent, for S. granulatus and S. variegatus fruiting body extracts, respectively) in the ethyl acetate extracts. S. granulatus extracts demonstrated the widest range of antimicrobial effects against both gram-positive and gram-negative bacteria (from 11.7 ± 1.3 to 28.5 ± 3.3 mm against Pseudomonas aeruginosa and Bacillus mycoides, respectively); and against two fungal strains (up to 13.6 ± 0.4 mm on Meyerozyma guilliermondii) in agar disc diffusion tests. Our study revealed that methanolic extracts of the most tested Suillus sp. were not active enough against the tested parasites: Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum and Plasmodium falciparum. Only S. variegatus extracts showed good antiprotozoal effects against P. falciparum (12.70 µg/mL). Cytotoxic activity was observed on human diploid lung cells MRC-5 SV2 by S. granulatus extracts (64.45 µg/mL). For comparative purposes, extracts of other common Lithuanian fungi, such as Xerocomus sp. (X. badius, X. chrysenteron and X. subtomentosus), Tylopilus felleus, Phallus impudicus and Pycnoporus cinnabarinus were investigated for their activity. The P. cinnabarinus extracts demonstrated the highest and broadest overall effects: 1.32 µg/mL against T. brucei, 1.46 µg/mL against P. falciparum, 3.93 µg/mL against T. cruzi and 21.53 µg/mL against L. infantum. Additionally, this extract exhibited strong cytotoxicity on MRC-5 cells (13.05 µg/mL). The investigation of bioactive fungal metabolites is important for the development of a new generation of antioxidants, antimicrobials, antiparasitic and anticancer agents. Full article

Plasmodium, Leishmania, and Trypanosoma parasites are responsible for infectious diseases threatening millions of people worldwide. Despite more recent efforts devoted to the search for new antiprotozoal agents, efficacy, safety, and resistance issues still hinder the development of suited therapeutic options. The lack of robustly validated targets and the complexity of parasite’s diseases have made phenotypic screening a preferential drug discovery strategy for the identification of new chemical entities. However, via this approach, no information on biological target(s) and mechanisms of action of compounds are provided. Among the target deconvolution strategies useful to fill this gap, photoaffinity labeling (PAL) has emerged as one of most suited to enable investigation in a complex cellular environment. More recently, PAL has been exploited to unravel the molecular basis of bioactive compounds’ function in live parasites, allowing elucidation of the mechanism of action of both approved drugs and new chemical entities. Besides highlighting new potential drug targets, PAL can provide valuable information on efficacy and liabilities of small molecules at the molecular level, which could be exploited to greatly facilitate the rational optimization of compounds in terms of potency and safety. In this review, we will report the most recent studies that have leveraged PAL to disclose the biological targets and mechanism of action of phenotypically active compounds targeting kinetoplastid diseases (i.e., human African trypanosomiasis, leishmaniasis, and Chagas disease) and malaria. Moreover, we will comment on potential perspectives that this innovative approach can provide in aiding the discovery and development of new antiprotozoal drugs. Full article

Veterinary drugs are extensively utilized in poultry farming for purposes such as disease prevention, disease treatment, and feed efficiency enhancement. However, the application of these drugs can lead to unacceptable residues in edible products. This study aimed to investigate the residue profiles of veterinary drugs in silkie chickens. A total of 130 chicken samples were collected from two major retail markets in Taiwan between 2022 and 2024. The analysis of drug residues was conducted using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). The overall detection rate of drug residues was 57.7%, and most of these residues were found to be below the maximum residue limits. Among the detected drugs, trimethoprim was the most prevalent, followed by nicarbazin, robenidine, decoquinate, diclazuril, and sulfamonomethoxine. Notably, there was a 31.4% chance that different samples from the same flock would yield varying results. Furthermore, a positive correlation was observed between drug residues and sample weight. In conclusion, this study provides valuable epidemiological data on drug residue profiles in silkie chickens in Taiwan. In the future, it is highly recommended that veterinary drug residues be continuously monitored, and food product sampling protocols be adjusted annually to ensure ongoing compliance with safety standards and protect consumer health. Full article

Background: Leishmaniasis, caused by Leishmania protozoa and transmitted by vectors, presents varied clinical manifestations based on parasite species and host immunity. The lack of effective vaccines or treatments has prompted research into new therapies, including thiourea derivatives, which have demonstrated antiprotozoal activities. Methods: We synthesized two series of N,N′-disubstituted thiourea derivatives through the reaction of isothiocyanates with amines. These compounds were evaluated in vitro against promastigote and amastigote forms of L. amazonensis, alongside cytotoxicity assessments on macrophages. In silico studies were conducted to analyze structure–activity relationships (SARs) and drug-likeness. Results: A total of fifty thiourea derivatives were synthesized and tested. Compound 3e from the first generation exhibited significant anti-leishmanial activity with an IC₅₀ of 4.9 ± 1.2 µM and over 80-fold selectivity compared to that of miltefosine (IC₅₀ = 7.5 ± 1.2 µM). The introduction of a piperazine ring in the second-generation thioureas enhanced potency and selectivity, with compound 5i achieving an IC₅₀ of 1.8 ± 0.5 µM and a selectivity index of approximately 70. Pharmacokinetic predictions indicated favorable profiles for the active compounds. Conclusions: SAR and ADMET analyses identified compound 5i as the most promising candidate for further preclinical evaluation, suggesting that piperazine thiourea derivatives represent a novel class of anti-leishmanial agents. Full article

Metallodrugs represent a critical area of medicinal chemistry with the potential to address a wide range of diseases. Their design requires a multidisciplinary approach, combining principles of inorganic chemistry, pharmacology, and molecular biology to create effective and safe therapeutic agents. Vanadium, the element of the fifth group of the first transition series (3d metals), has been already detected as a crucial species in the biological action of some enzymes, e.g., nitrogenases and chloroperoxidase; furthermore, vanadium-based compounds have recently been described as physiologically stable with therapeutic behavior, e.g., having anticancer, antidiabetic (insulin-mimicking), antiprotozoal, antibacterial, antiviral, and inhibition of neurodegenerative disease properties. Since the binding of metallodrugs to serum albumin influences the distribution, stability, toxicity (intended and off-target interactions), and overall pharmacological properties, the biophysical characterization between serum albumin and vanadium-based compounds is one of the hot topics in pharmacology. Overall, since vanadium complexes offer new possibilities for the design of novel metallodrugs, this review summarized some up-to-date biological and medicinal aspects, highlighting proteins as the main targets for the inorganic complexes based on this transition metal. Full article

Background/Objectives: In this study, the efficacy of benzo[h]chromene derivatives as antiprotozoal and antimycobacterial agents was explored. Methods: A total of twenty compounds, including benzo[h]chromene alkyl diesters and benzo[h]chromene-triazole derivatives, were synthesized and tested against Trypanosoma cruzi, Leishmania braziliensis, L. infantum, and strains of Mycobacterium abscessus and Mycobacterium intracellulare LIID-01. Notably, compounds 1a, 1b, 2a, and 3f exhibited superior activity against Trypanosoma cruzi, with IC₅₀ values of 19.2, 37.3, 68.7, and 24.7 µM, respectively, outperforming the reference drug benznidazole (IC₅₀: 54.7 µM). Results: Compounds 1b and 3f showed excellent selectivity indices against Leishmania braziliensis, with SI values of 19 and 18, respectively, suggesting they could be potential alternatives to the commonly used, but more selective, miltefosine (IC₅₀: 64.0 µM, SI: 43.0). Additionally, compounds 1a, 1b, and 3f were most effective against Leishmania infantum, with IC₅₀ values of 24.9, 30.5, and 46.6 µM, respectively. Compounds 3f and 3h were particularly potent against various Mycobacterium abscessus strains, highlighting their significance given the inherent resistance of these bacteria to standard antimicrobials. Conclusions: The sensitivity of Mycobacterium intracellulare LIID-01 to these compounds also underscored their potential in managing infections by the Mycobacterium avium–intracellulare complex. Full article

Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against L. amazonensis, L. infantum, and L. mexicana. In vitro, cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for all compounds, and those showing adequate activity and selectivity were tested against intracellular amastigotes. Transmission and scanning electron microscopy were employed to study the effects of 3-alkoxy-1-benzyl-5-nitroindazole and 2-benzyl-5-nitroindazolin-3-one derivatives on promastigotes of L. amazonensis. Compounds NV6 and NV8 were active in the two life stages of the three species, with the latter showing the best indicators of activity and selectivity. 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) showed in vitro activity comparable to that of amphotericin B against the promastigote stage of Leishmania spp. Two compounds were also found to be active the amastigote stage. Electron microscopy studies confirmed the antileishmanial activity of the indazole derivatives studied and support future research on this family of compounds as antileishmanial agents. Full article

Naphthylimides play a pivotal role as aromatic heterocyclic compounds, serving as the foundational structures for numerous pharmacologically significant drugs. These drugs encompass antibacterial, antifungal, anticancer, antimalarial, antiviral, anti-inflammatory, antithrombotic, and antiprotozoal agents. The planar and heteroaromatic characteristics of naphthylimides grant them a strong ability to intercalate into DNA. This intercalation property renders naphthylimide derivatives highly valuable for various biological activities. The advantageous pharmacological activity and ease of synthesis associated with naphthylimides and their derivatives provide significant benefits in the design and development of new compounds within this class. Currently, only a few such molecules are undergoing preclinical and clinical evaluations. In this paper, we have compiled the literature on naphthylimides reported by researchers from 2006 to 2024. Our focus lies on exploring the pharmacological activities of their analogues from a drug development and discovery perspective, while examining their structure–activity relationship and mechanisms of action. Full article

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease in humans. The current antichagasic drugs nifurtimox and benznidazole have inconveniences of toxicity; therefore, the search for alternative therapeutic strategies is necessary. The present study reports the synthesis, drug-likeness predictions, and in vitro anti-trypanosome activity of a series of 14 quinazoline 2,4,6-triamine derivatives. All compounds were tested against T. cruzi (epimastigotes and trypomastigotes) and in HFF1 human foreskin fibroblasts. The bioassays showed that compounds 2–4 containing nitrobenzoyl substituents at 6-position of the quinazoline 2,4,6-triamine nucleus were the most potent on its antiprotozoal activity. The effect was observed at 24 h and it was preserved for at least 5 days. Also, compounds 2–4 were not toxic to the human control cells, showing high selectivity index. The quinazoline nitro derivatives have potential use as antichagasic agents. Full article

Cestodes are etiological agents of neglected diseases such as echinococcosis and cysticercosis, which are major public health problems. Antiparasitic treatment relies on a small number of approved drugs, which are often only partially effective, poorly tolerated and require prolonged administration. Thus, the discovery of novel potential treatments is critical. The Stevia genus (Asteraceae) includes species that are recognized as a source of bioactive compounds, with many species associated with medicinal uses. In this study, the cestocidal activity of four South American Stevia species that previously showed antiprotozoal activity was analyzed using a motility assay on the laboratory cestode model, Mesocestoides vogae. The four Stevia extracts showed cestocidal activity, with S. alpina var. alpina as the most active. The sesquiterpene lactones estafietin and eupatoriopicrin were purified from S. alpina var. alpina and S. maimarensis, respectively, and tested on M. vogae. Estafietin showed cestocidal activity, inhibiting parasite viability in a dose-dependent manner, even from the first day of incubation. Consistent with the motility effects, the extract of S. alpina var. alpina and estafietin induced marked alterations in the morphology of the parasite. The results of this report show that Stevia species represent a source of new molecules with potential for the treatment of neglected tropical diseases caused by cestodes. Full article

Background/Objectives: While multiple studies have investigated antibiotic consumption rates, there are few studies on the consumption of systemic antifungals and antiprotozoals. This study aims to fill this gap by providing a comprehensive analysis of nationwide consumption trends in Kazakhstan over a seven-year period (2017–2023). Methods: Defined daily doses per 1000 inhabitants per day were calculated for systemic antifungals (J02 code of the Anatomical Therapeutic Chemical Classification System (ATC)) and antiprotozoals (P01 code of the ATC). Time series analyses were applied to examine historical trends, evaluate the impact of the COVID-19 pandemic, and make future projections until 2030. Results: The total consumption increased over the study period, with an average annual percent change of 1.11% for antifungals and 5.48% for antiprotozoals. Fluconazole was the most consumed antifungal agent, whereas metronidazole was the most consumed antiprotozoal agent. The COVID-19 pandemic had a positive but insignificant effect on the consumption of antifungals and a negative and also insignificant effect on the consumption of antiprotozoals. Forecast modeling indicates that the future trends in antifungal and antiprotozoal consumption until 2030 will largely remain stable, with the exception of antiprotozoal consumption in the hospital sector, which is projected to decline. Conclusions: These findings offer valuable insights into the development and implementation of targeted antimicrobial stewardship programs in Kazakhstan. Full article

Cryptosporidium parvum (C. parvum) is one of the most prevalent species infecting humans and animals. Currently, the only FDA-licensed drug to treat cryptosporidiosis is nitazoxanide (NTZ), with no efficacy in immunocompromised hosts. Citrus paradisi (C. paradisi) has demonstrated anti-protozoal activities. This study aimed to investigate the anti-cryptosporidiosis effect of C. paradisi peel extract, either alone or in mediating the green synthesis of chitosan silver nanoparticles (Cs/Ag NPs), compared to NTZ. Mice were sorted into nine different groups. The effectiveness of the treatments was evaluated using parasitology, histopathology, immunohistochemistry, and immunology. C. paradisi outperformed nitazoxanide regarding oocyst shedding (79% vs. 61%). The effectiveness of NTZ Cs/Ag NPs and Citrus Cs/Ag NPs was enhanced to 78% and 91%, respectively. The highest oocyst inhibition was obtained by combining NTZ and Citrus Cs/Ag NPs (96%). NF-κB, TNF-α, and Il-10 levels increased in response to infection and decreased in response to various treatments, with the highest reduction in the group treated with combined NTZ citrus Cs/Ag NPs. Combining C. paradisi with NTZ could have a synergistic effect, making it a potentially effective anti-cryptosporidiosis agent. Utilizing C. paradisi in the green synthesis of Cs/Ag NPs improves the therapeutic response and can be used to produce novel therapeutic antiparasitic drugs. Full article

Kallopterolides A–I (1–9), a family of nine diterpenoids possessing either a cleaved pseudopterane or a severed cembrane skeleton, along with several known compounds were isolated from the Caribbean Sea plume Antillogorgia kallos. The structures and relative configurations of 1–9 were characterized by analysis of HR-MS, IR, UV, and NMR spectroscopic data in addition to computational methods and side-by-side comparisons with published NMR data of related congeners. An investigation was conducted as to the potential of the kallopterolides as plausible in vitro anti-inflammatory, antiprotozoal, and antituberculosis agents. Full article