Antiparasitic Activity Research Articles

Antiparasitic Activities of Acyl Hydrazones from Cinnamaldehydes and Structurally Related Fragrances

Antiparasitic Activities of Acyl Hydrazones from Cinnamaldehydes and Structurally Related Fragrances

Evaluating the impact of Xanthoparmelia conspersa extracts on signaling in HeLa cells and exploring their diverse biological activities

Xanthoparmelia conspersa is rich in specific secondary metabolites but an unexplored lichen species. This work determined the chemical composition and biological activities (anti-microbial, anti-protozoal, and cytotoxic) of its methanolic and hexane extracts. Additionally, we evaluated the potential of these extracts in modulating cancer signaling pathways in HeLa cells. The phytochemical analysis revealed that usnic acid was the predominant constituent in the hexane extract, while stictic acid was in the methanolic one. Among tested cell lines (VERO, FaDu, SCC-25, HeLa), cytotoxic selectivity was detected for X. conspersa hexane extract against the FaDu (SI 7.36) and HeLa (SI 2.19) cells. A noticeably better anti-microbial potential was found for hexane extract, however, the overall anti-microbial activity was relatively weak (28, 21, and 20% inhibition of Candida glabrata, Cryptococcus neoformans, and Escherichia coli, respectively). On the contrary, the anti-parasitic action of hexane extract was significant, with an IC50 value of 2.64 µg/mL against Leishmania donovani – amastigote and 7.18 µg/mL against Trypanosoma brucei. The detailed evaluation of the cancer-related signaling pathways in HeLa cells, done by two distinct methodologies (luciferase reporter tests), revealed that especially the hexane extract and usnic acid exhibited selective inhibition of Stat3, Smad, NF-κB, cMYC, and Notch pathways.

Brazilian red propolis reduces the adhesion of oral biofilm cells and the Toxoplasma gondii intracellular proliferation

Infectious diseases remain as a significant cause of thousands of deaths annually worldwide. Therefore, this study aimed to investigate the antimicrobial and antiparasitic activity of the crude hydroalcoholic extract and compounds isolated from Brazilian Red Propolis (BRP) against oral pathogens and Toxoplasma gondii, using in vitro, in vivo and in silico approaches. Antimicrobial and synergistic activities were determined using the broth dilution method and the checkerboard assay, respectively. Antibiofilm activity was evaluated by staining with 2 % crystal violet and counting microorganisms. In vivo infection was carried out in Caenorhabditis elegans AU37 larvae and in silico analysis was performed using molecular docking simulations. The effect on growth modulation of T. gondii was evaluated through a β-galactosidase colorimetric assay. Minimum Inhibitory Concentration values ranged from 3.12 to 400 µg/mL. Biofilm Minimum Inhibitory Concentration (MICB50) values ranged from 6.25 to 375 µg/mL, with a significant reduction in the number of viable cells. Furthermore, Guttiferone E and the crude extract reduced cell aggregation and caused damage to the biofilm cell wall. The highest concentrations of the crude extract and Guttiferone E increased the survival and reduced the risk of death of infected and treated larvae. Guttiferone E and Oblongifolin B inhibited the intracellular proliferation of T. gondii and demonstrated several targets of action against bacteria and T. gondii through in silico analysis. These data demonstrate that BRP has antimicrobial and antiparasitic activity against pathogens of clinical relevance, and can be used in the future as phytomedicines.

Heterojunction of titanate nanotubes enhanced by curcumin: synthesis, characterization, and evaluation of hemolytic activity and cytotoxicity

Curcumin, the active compound of turmeric (Curcuma longa L.), is responsible for various therapeutic properties of the plant, such as anticancer, antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal, antiparasitic, wound-healing, and digestive activities, among others. In vitro studies have revealed that curcumin exhibits no toxicity against human red blood cells, highlighting its biological safety. A daily dose of up to 12g/day does not cause adverse effects in healthy individuals. However, despite good oral tolerance, its low bioavailability limits its applications, which can be overcome by incorporating curcumin powder (CCMP) into nanoformulations. Many studies have been reported with the aim of improving the bioavailability of CCMP using nanoformulations. However, there still need to be reports on using titanate nanotubes for this purpose. This work aimed to formulate a nanocomposite between sodium titanate nanotubes (NaTiNT) and CCMP. The NaTiNTs were synthesized using the alkaline hydrothermal method and subjected to heterojunction with CCMP, forming the NaTiNT@CCMP sample. The structural characterization of the material was carried out using XRD, FT-IR, TG, XPS, and TEM techniques, which confirmed the union and the intact physical integrity of both after the junction. The results obtained from thermogravimetric analysis demonstrated the thermal stability that CCMP acquired upon bonding with the titanate nanotubes. XPS detected the bond formed between CCMP and the titanium of NaTiNTs. The biological evaluation was conducted through in vitro assays of Residual Hemolytic Activity (%HR) and cytotoxicity assessment (MTT), which was performed with rat bone marrow mesenchymal stem cells (BMMSCs). The biological test results showed that the NaTiNT sample exhibited hemolytic activity at 50mgmL-1. In comparison, the CCMP sample showed reduced viability at 50mgmL-1 and 25mgmL-1 concentrations and slightly reduced viability at 6.25mgmL-1. The NaTiNT@CCMP sample, on the other hand, did not have hemolytic activity at any of the concentrations studied. In the cytotoxicity test, samples with varying concentrations of NaTiNT and CCMP demonstrated reduced overall viability over 48hours. However, in the meantime, the heterojunction of the two samples, at most concentrations used, exhibited viability similar to that of the control and did not show cytotoxicity to the cells studied. In summary, the heterojunction of the two structures leads to low hemolytic activity and minimal cytotoxicity compared to both isolated structures.

Therapeutic Potential of Aryl Sulfonamides: Synthesis, Antiproliferative, Antioxidant, Antiparasitic and Molecular Docking Studies

AbstractThis study outlines the synthesis of pyrazine sulfonamides (3 a–3 i) along with halo‐phenyl derivatives (4 a–4 j and 5 a–5 e). The antiproliferative effects were tested against MCF‐7 breast cancer, and colon carcinoma HT‐29, HCT‐116 WT, and HCT‐116 p53 knock‐out mutant cell lines. Compounds 3 b and 3 c were notably active against HCT‐116 WT cells, while 3 e and 3 h were moderately effective against MCF‐7 cells. Among the halo‐phenyl sulfonamides, 4e and 4j were active against MCF‐7 cells, and 5 b was active against HCT‐116 WT cells. The most promising compounds were evaluated against non‐tumorigenic cells, demonstrating cancer selectivity. Compounds 3 b, 3 c, 3 e, 3 h, and 5 b showed dose‐dependent inhibition of colony formation. Compound 3 f exhibited free radical scavenging activity comparable to ascorbic acid. Molecular docking revealed strong binding to thymidylate synthase (3 b, 5 b), Akt‐3 protein kinase (3 e, 3 h, 4 e, 4 j), and tyrosinase (3 f, 3 h). The compounds also exhibited antiparasitic activity against Toxoplasma gondii and Leishmania major, with modifications enhancing selectivity for T. gondii. Substitutions in compounds 4 b and 4 d increased activity against T. gondii while reducing toxicity. Notably, compound 4 f emerged as a T. gondii‐selective lead drug. These findings suggest sulfonamides may help treat complex diseases like cancer and infections.

Antimicrobial Potential of Scorpion-Venom-Derived Peptides.

The frequent and irrational use of antibiotics by humans has led to the escalating rise of antimicrobial resistance (AMR) with a high rate of morbidity-mortality worldwide, which poses a challenge to the development of effective treatments. A large number of host defense peptides from different organisms have gained interest due to their broad antibacterial spectrum, rapid action, and low target resistance, implying that these natural sources might be a new alternative to antimicrobial drugs. As important effectors of prey capture, defense against other animal attacks, and competitor deterrence, scorpion venoms have been developed as important candidate sources for modern drug development. With the rapid progress of bioanalytical and high throughput sequencing techniques, more and more scorpion-venom-derived peptides, including disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs), have been recently identified as having massive pharmacological activities in channelopathies, pathogen infections, and cancer treatments. In this review, we summarize the molecular diversity and corresponding structural classification of scorpion venom peptides with antibacterial, antifungal, and/or antiparasitic activity. We also aim to improve the understanding of the underlying mechanisms by which scorpion-venom-derived peptides exert these antimicrobial functions, and finally highlight their key aspects and prospects for antimicrobial therapeutic or pharmaceutical application.

Ganoderma lucidum triterpenoids investigating their role in medicinal applications and genomic protection.

Ganoderma lucidum (GL) is a white rot fungus widely used for its pharmacological properties and health benefits. GL consists of several biological components, including polysaccharides, sterols, and triterpenoids. Triterpenoids are often found in GL in the form of lanostane-type triterpenoids with quadrilateral carbon structures. The study revealed that triterpenoids have diverse biological properties and can be categorized based on their functional groups. Triterpenoids derived from GL have shown potential medicinal applications. They can disrupt the cell cycle by inhibiting β-catenin or protein kinase C activity, leading to anti-cancer, anti-inflammatory, and anti-diabetic effects. They can also reduce the production of inflammatory cytokines, thus mitigating inflammation. Additionally, triterpenoids have been found to enhance the immune system's defenses against various health conditions. They possess antioxidant, antiparasitic, anti-hyperlipidemic, and antimicrobial activities, making them suitable for pharmaceutical applications. Furthermore, triterpenoids are believed to afford radioprotection to DNA, protecting it from radiation damage. This review focuses on the types of triterpenoids isolated from GL, their synthesis pathways, and their chemical structures. Additionally, it highlights the pharmacological characteristics of triterpenoids derived from GL, emphasizing their significant role in various therapeutic applications and health benefits for both humans and animals.

Antioxidant and anti-glycation activities of Mandevilla velutina extract and effect on parasitemia levels in Trypanosoma cruzi experimental infection: In vivo, in vitro and in silico approaches

Ethnopharmacological relevanceMandevilla velutina (Mart. Ex Stadelm.) Woodson, known in Brazil as "infalível" and "jalapa", is a medicinal plant native from the Cerrado region (Brazilian Savannah). The underground organ (xylopodium) of this species is prepared as ethanolic extract or infusion and it is commonly used in traditional medicine to treat snake venom. Although, locals and indigenous populations from Cerrado have used M. velutina for the treatment of infection by Trypanosoma cruzi (Chagas’ disease). Aim of the studyThis study aimed to evaluate the in vitro antioxidant and anti-glycation activities of the crude hydroethanolic extract of M. velutina xylopodium. Besides, it aimed to evaluate its effect on parasitemia levels in vivo T. cruzi experimental infection. In addition, this study aimed to determine possible interactions between the main compound of the extract and molecular targets associated with survival and virulence of T. cruzi in silico approaches. Materials and methodsDetermination of total polyphenols, flavonoids and steroidal aglycones content were performed. In addition, high performance liquid chromatography (HPLC) was carried out to identify main compounds of the extract. Antioxidant activity was determined by DPPH radical scavenging, ferric ion reducing power (FRAP), Thiobarbituric acid reactive species (TBARS) and Oxygen Radical Absorbance Capacity (ORAC) methods. Anti-glycation activity was demonstrated through relative mobility in electrophoresis (RME), determination of free amino groups and inhibition of AGEs formation. Determination of the action of extract in parasitemia levels was performed by T. cruzi experimental infection of mice and nitrite levels were measured in the serum of animals evaluated in this study. Molecular docking analyses of the main compound (Velutinol A) with DNA and molecular targets associated with survival and virulence of T. cruzi. ResultsPhytoconstituents evaluation exhibited the presence polyphenols, flavonoids and steroidal aglycone, and HPLC identified the major presence of Velutinol A. Antioxidant and anti-glycation evaluations showed that the extract present significant activity in all methods evaluated. In addition, extract reduced the number of trypomastigotes and increased the survival of treated animals. The treatment using extract showed an interference in the synthesis of physiological nitric oxide as an immune response to infection. In silico assays demonstrated interaction between Velutinol A and DNA and molecular targets of T. cruzi. ConclusionsThe results showed that the hydroethanolic extract of M. velutina xylopodium contains bioactive compounds including polyphenols, flavonoids and steroidal aglycones (mainly Velutinol A) of which may be responsible for the antioxidant, anti-glycation and anti-parasitic activity against T. cruzi. Trypanocidal activity of M. velutina compounds may be linked to their influence on NO synthesis during infection and/or their capacity to bind and inhibit molecules associated to virulence and survival of T. cruzi.

Therapeutic effect of topical tamoxifen in murine cutaneous leishmaniasis caused by Leishmania major.

Iran is one of the endemic regions of cutaneous leishmaniasis (CL) caused by Leishmania major. There is no protective vaccine available against CL available, and the most effective strategy is a definitive treatment. Topical medications can be an excellent option for this purpose. Tamoxifen, a cancer control drug, has properties such as inducing cell apoptosis and anti-parasitic activity, which can be useful in controlling eukaryotic parasites such as Leishmania. The present study was conducted to investigate this theory in experimental CL caused by L. major. Forty female BALB/c mice aged 4 to 6 weeks were infected by injecting 1 × 106 L. major metacyclics (MRHO/IR/75/ER) in the base of the tail. After the appearance of Leishmania nodules, mice were divided into five test and control groups. Two drug formulations were used: tamoxifen 1% in ethanol and tamoxifen citrate ointment 0.1%. The effectiveness of each formula was evaluated by determining the mean size of the ulcers and parasite burden after a 28-day treatment period. Both formulations showed reduced ulcer mean sizes. However, only the tamoxifen citrate ointment group demonstrated a statistically significant reduction (P = 0.049). The parasite burden decreased by 40.83% for the ointment group and 33.67% for the ethanol solution. Other control groups showed lesser reductions. This study partially demonstrated the effectiveness of topical tamoxifen on CL lesions in a murine model. It can provide a basis for further research on the therapeutic effects of different topical tamoxifen formulations.

From clove oil to bioactive agents: synthetic routes, antimicrobial and antiparasitic activities of eugenol derivatives.

Eugenol, a natural compound found in essential oils such as clove oil, has been extensively studied for its diverse biological activities including the therapeutic potential against microbial and parasitic infections. This review provides an overview of the synthetic strategies (shown in Supplementary Material) employed to develop bioactive derivatives and analogues derived from eugenol and related compounds (e.g., dihydroeugenol and isoeugenol), focusing on biological activity of more than 100 bioactive eugenol derivatives against bacterial, fungal, viral and protozoal pathogens. Through a comprehensive survey of literature, this paper shows the impact of structural modifications of these phenylpropanoids on antimicrobial and antiparasitic activity. Key findings highlight promising candidates for further development in antimicrobial drug discovery, suggesting directions for future research in the pursuit of effective therapeutic agents.

Therapeutic applications of Eugenia klotzschiana O.Berg: A Systematic Bibliographic Review

Eugenia klotzschiana O.Berg is an endemic plant from the Brazilian Cerrado biome with substantial chemical and genomic diversity. This systematic review aimed to identify the therapeutic applications of the plant in the SciELO, Bireme, LILACS, PubMed/Medline, Web of Science, Google Scholar, and Science Direct bibliographic databases, using the START Program for identifying and selecting studies. Forty-six articles were obtained, of which 42 were excluded, and four were included in the review. The described therapeutic applications were antioxidant, antimicrobial, antiparasitic, and cytotoxic activities of fruits, flowers, and leaves. The small number of published articles indicates the need for developing studies on the therapeutic potential of E. klotzschiana O. Berg.

Insight into the therapeutic potential of pyrazole-thiazole hybrids: A comprehensive review.

Several pyrazole-thiazole hybrids featuring two potentially bioactive pharmacophores with or without linker have been synthesized using the molecular hybridization approach as target structures by medicinal chemists to modulate multiple drug targets simultaneously. The presented review aims to provide an overview of the diversified and wide array of pharmacological activities of these hybrids bestowing anticancer, antifungal, antibacterial, analgesic, anti-inflammatory, antioxidant, antitubercular, antiviral, antiparasitic, and miscellaneous activities. The structure-activity relationships and potential mechanism of action are also reviewed to shed light on the development of more effective and biotargeted candidates. This review focuses on the latest research advances in the biological profile of pyrazole-thiazole hybrids reported from 2015 to the present, providing medicinal researchers with a comprehensive platform to rationally design and develop more promising pyrazole-thiazole hybrids.

Exploring the Antibacterial and Antiparasitic Activity of Phenylaminonaphthoquinones-Green Synthesis, Biological Evaluation and Computational Study.

Organic compounds with antibacterial and antiparasitic properties are gaining significance for biomedical applications. This study focuses on the solvent-free synthesis (green synthesis) of 1,4-naphthoquinone or 2,3-dichloro-1,4-naphthoquinone with different phenylamines using silica gel as an acid solid support. The study also includes in silico PASS predictions and the discovery of antibacterial and antiparasitic properties of phenylaminonaphthoquinone derivatives 1-12, which can be further applied in drug discovery and development. These activities were discussed in terms of molecular descriptors such as hydrophobicity, molar refractivity, and half-wave potentials. The in vitro antimicrobial potential of the synthesized compounds 1-12 was evaluated against a panel of six bacterial strains (three Gram-positive: Staphylococcus aureus, Proteus mirabilis, and Enterococcus faecalis; and three Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, and Klebsiella pneumoniae). Six compounds (1, 3, 5, 7, 10, and 11) showed better activity toward S. aureus with MIC values between 3.2 and 5.7 μg/mL compared to cefazolin (MIC = 4.2 μg/mL) and cefotaxime (MIC = 8.9 μg/mL), two cephalosporin antibiotics. Regarding in vitro antiplasmodial activity, compounds 1 and 3 were the most active against the Plasmodium falciparum strain 3D7 (chloroquine-sensitive), displaying IC50 values of 0.16 and 0.0049 μg/mL, respectively, compared to chloroquine (0.33 μg/mL). In strain FCR-3 (chloroquine-resistant), most of the compounds showed good activity, with compounds 3 (0.12 μg/mL) and 11 (0.55 μg/mL) being particularly noteworthy. Additionally, docking studies were used to better rationalize the action and prediction of the binding modes of these compounds. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed.

Design and Synthesis of Benzimidazole Carboxamide Cysteine Protease Inhibitors as Promising Anti-leishmanial Agents.

More than 20 protozoan species of Leishmania are responsible for causing Leishmaniasis, an infection spread by blood-feeding phlebotomine sandflies. A narrow pool of drugs is currently available rendering the current drug stratagem to treat this infection . Development of novel, less toxic, and more effective regimens is thus a need of the hour. Design and synthesis of benzo[d]imidazole carboxamides as agents to combat Leishmaniasis are also required. 14 benzo[d]imidazole carboxamides were synthesized and gauged against L. donovani promastigotes and intramacrophage amastigote forms. All of the tested compounds exhibited significant anti-promastigote properties with IC50 well below 10 uM. Compounds 4a, 4b, and 4d, showing the highest anti-parasitic activity against promastigote forms (IC50 0.91- 1.33 μM), were also found to be associated with better anti-leishmanial potential (IC50 0.78- 1.67 μM) against the intramacrophage amastigotes comparable to Amphotericin-B (0.13 μM), a drug used for Leishmaniasis. Compound (4a), namely N-(2-(trifluoromethyl)-1Hbenzo[ d]imidazol-5-yl)benzo[d][1,3]-5-carboxamide-dioxole, was found to be most potent against L. donovani amastigotes among all the tested compounds, and demonstrated better antileishmanial properties (IC50 0.78 μM) when compared to the standard. Compound 4a was also assessed for its toxicity profile against THP-1 human monocytic cells. To establish the molecular target(s) in silico, molecular docking studies were performed against cysteine protease, a putative virulence factor of Leishmania parasites, and nucleoside diphosphate kinase, an enzyme with a critical role in nucleotide recycling, also associated with resistance in Leishmania strains. Compound 4a showed better binding affinity than the standard to these targets; furthermore, the molecular dynamic simulation studies further affirmed the stability of compound 4a, within the active site of the targets. In vitro, cysteine protease inhibitory activity (IC50 8.53 μM) using Bz-Arg-AMC hydrochloride fluorogenic peptide substrate established the promising potential of 4a as a cysteine protease inhibitor. Computational ADMET analysis indicated appropriate pharmacokinetic profile and physicochemical characteristics for all members of the synthesized library. Both in vitro and in silico studies indicate that the synthesized imidazole carboxamides can act as potent hits and that N-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5- yl)benzo[d][1,3]-5-carboxamide-dioxole 4a can be an effective hit molecule which can be further developed into potent lead molecule (s) to fight Leishmania donovani.

Estimation of antiparasitic activity of fungal extracts towards Leishmania donovani in murine model

Background. Fungi produce many compounds have pharmaceutical usage. The current study was aimed to extract therapeutic compounds from fungi that grow in critical conditions and fungi that can be produced commercially which may have potential therapeutic activities against Leishmania donovani. The current study was aimed to extract therapeutic compounds from fungi that grow in critical conditions and fungi that can be produced commercially which may have potential therapeutic activities against Leishmania donovani. Methods. Two fungal isolates were used to evaluate antileishmanial activities of their extracts, the first due to Aspergillus terreus was isolated from salty sediments, while another represented local edible mushroom of Agaricus bisporus. The experiment was conducted in vivo after four weeks infection of Leishmania donovani. Infected mice were treated intraperitonially with 2 and 4 mg/kg daily for 10 days. Result. All compound has a significant effect on the viability and decrease the number of parasites in animal in comparison with pentostam, as well as, the M19 was appeared with highest effect in both concentrations. The method of examining infected tissues had a role in determining the number of parasites without affecting the percentage of presence in different treatments, as the numbers of parasites calculated in the tissue sections are more realistic than the number of parasites calculated in the printing method, as counting the parasite with tissue sections gives an impression of the spatial distribution of the parasite, whether within tissues or body fluids, unlike the printing method, which shows the presence of the parasite in body fluids and immune cells thus be suitable for the diagnosis of parasite amastigote in vivo. Conclusion. The compound extracted during study and diagnoses by GC-Mass technique are promising applicants for research on new drugs with anti-Leishmania activity derived from natural products.

Bis-Chalcones: Recent Reports of Their Diverse Applications in Biological and Material Sciences.

Originating from the basic chalcone structure, bis-chalcones are characterized by their dual α,β-unsaturated carbonyl systems and carry a range of biological activities that include antimicrobial, antiviral, antiparasitic, antioxidant, antiproliferative, and chemical reactivities that warrant a review to cover recent progress. Thus, this review presents the significant potential demonstrated by bis-chalcones in various biological applications. For example, compounds 2.3.1 showed excellent antiparasitic activity against leishmania with good selectivity index, and compounds 2.2.1-2.2.3 showed submicromolar activity against SupT1 cells. Compound 2.6.22 stood out in its antiproliferative activity against a panel of 60 different cell lines. Compounds 2.6.4 and 2.6.9 have been shown as submicromolar noncompetitive xanthine oxidase inhibitors. We also present their recent applications in material science, for example, as photosensitizers and photoinitiators, to showcase their broader potential for innovation in both medicinal chemistry and industrial applications.

α-costic acid, the main sesquiterpenoid isolated from Dittrichia viscosa (L) Greuter, induces oxidative stress and autophagy in tomato.

Dittrichia viscosa (L.) Greuter, a perennial plant in the Asteraceae, has strong allelopathic activity due to the high content of various secondary metabolites. The bicyclic sesquiterpenoid α-costic acid is the most abundant secondary metabolite of D. viscosa. Its remarkable insecticidal, antiparasitic, and phytotoxic activities point to its potential use as a natural herbicide, but information on its mode of action is lacking. To shed light on the mechanism of action of α-costic acid in plant cells, we investigated the phytotoxicity of α-costic acid in tomato plants (Solanum lycopersicum L.) through in vivo assays, the underlying cellular effects using biochemical assays, and the effect on subcellular organelles using confocal microscopy on tomato protoplasts incubated with organelle-specific fluorescent probes. In vivo tests showed that α-costic acid inhibited the growth of tomato seedlings and induced chlorosis and spot lesions in leaves. Biochemical assays demonstrated that α-costic acid caused ion leakage, chlorophyll depletion, H2O2 overproduction, callose deposition, and membrane lipid peroxidation. Confocal microscopy demonstrated that α-costic acid determined ROS overproduction and network disruption in mitochondria, singlet oxygen overproduction in chloroplasts, vacuole disintegration, and autophagosome formation. Overall, our data are consistent with a model according to which α-costic acid phytotoxicity is related to oxidative stress in mitochondria and chloroplasts that induces extensive membrane damage, ultimately resulting in cell death associated with autophagy.

Antileishmanial, antitrypanosomal and anti-coronavirus activities of benzophenanthridine alkaloids and other specialized metabolites isolated from the root bark of Zanthoxylum zanthoxyloides (Lam.) B.Zepernick & Timler

Strong antileishmanial and antitrypanosomal activities were highlighted for the crude methanolic extract (IC50 = 0.61 and 2.15 μg/mL, respectively) of Zanthoxylum zanthoxyloides (Lam.) B.Zepernick & Timler root bark, as well as for its apolar partitions (cyclohexane: IC50 = 0.66 and 5.17 μg/mL, respectively and dichloromethane: IC50 = 0.07 and 0.22 μg/mL, respectively), with a good selectivity index (SI) towards WI-38 cells. In addition, cyclohexane and dichloromethane extracts exhibited a dose-dependent inhibition of human coronavirus HCoV-229E infection in hepatoma Huh-7 cells expressing or not the cellular protease TMPRSS2 (IC50 values of 5.29 μg/mL and 4.87 μg/mL, respectively). Fractionation of these active extracts led to the isolation of a new racemic benzophenanthridine alkaloid named zanthoxyloithrine (1), together with 13 known compounds. Their structures were elucidated by spectroscopic techniques including IR, UV, HR-MS, 1D and 2D NMR and electronic circular dichroism. In parallel, HR-ESI-MS/MS based dereplication and molecular networking analysis were performed to identify unpurified compounds in cyclohexane and dichloromethane extracts. Zanthoxyloithrine (1) showed strong antileishmanial (IC50 = 0.14 μM, SI = 52.0) and antitrypanosomal (IC50 = 0.36 μM, SI = 20.8) activities. In addition, compound (1) demonstrated a high antiviral activity against HCoV-229E with IC50 value of 6.70 μM in presence of TMPRRS2 and without significant toxicity on Huh-7 cells. Other purified benzo[c]phenanthridine alkaloids also showed anti-coronavirus and antiparasitic activities.

The importance of application of medicinal plants and natural products in poultry health management

Application of herbs and natural medicines have shown to have no negative side effects, with high effectiveness to improve productivity. Usage of medicinal plants can increase gut function, improve hepatic function, inhibition of prooxidant enzymes, enhance antioxidant content, improve shelf life, enhance sensorial value, better nutritive value, improve both health and consumers preference, enhance calcium and other minerals, increase vitamin B and folate, and enhance immunity. The most important medicinal plants with antiparasitic activities are green tea, guar bean, pine bark, grape seed, barberry root bark, Rangoon creeper, olive tree, and wormwood. Some other important medicinal plants in poultry industry are black pepper, nettle, shrubby sophora, Aleppo oak, garlic, red cedar, ginger, mint, tobacco, turmeric, aloe vera, etc. The application of herbal medicines can be considered as an important alternative to treating parasitic infections. In organic broiler production with application of medicinal plants, decreasing hormones, growth promoters and antibiotics should be considered as well as paying more attention to selection of appropriate organic feed management with considering higher production. This article aims to survey on the importance of application of natural products and medicinal plants in poultry industry by considering secondary metabolites such as triterpenoids, coumarins, alkaloids, tannins, and flavonoids due to their anti-inflammatory, antiparasitic, antimicrobial, antioxidant, and astringent properties.

Evaluating the potential of non-immunosuppressive cyclosporin analogs for targeting Toxoplasma gondii cyclophilin: Insights from structural studies.

Toxoplasmosis persists as a prevalent disease, facing challenges from parasite resistance and treatment side effects. Consequently, identifying new drugs by exploring novel protein targets is essential for effective intervention. Cyclosporin A (CsA) possesses antiparasitic activity against Toxoplasma gondii, with cyclophilins identified as possible targets. However, CsA immunosuppressive nature hinders its use as an antitoxoplasmosis agent. Here, we evaluate the potential of three CsA derivatives devoid of immunosuppressive activity, namely, NIM811, Alisporivir, and dihydrocyclosporin A to target a previously characterized cyclophilin from Toxoplasma gondii (TgCyp23). We determined the X-ray crystal structures of TgCyp23 in complex with the three analogs and elucidated their binding and inhibitory properties. The high resolution of the structures revealed the precise positioning of ligands within the TgCyp23 binding site and the details of protein-ligand interactions. A comparison with the established ternary structure involving calcineurin indicates that substitutions at position 4 in CsA derivatives prevent calcineurin binding. This finding provides a molecular explanation for why CsA analogs can target Toxoplasma cyclophilins without compromising the human immune response.