Parasitic diseases pose a major burden throughout the globe, especially in low-income countries, which are disproportionately affected due to factors such as overpopulation, vector-control challenges, financial difficult...Parasitic diseases pose a major burden throughout the globe, especially in low-income countries, which are disproportionately affected due to factors such as overpopulation, vector-control challenges, financial difficulties, etc. Because access to advanced diagnostic technologies is limited in low-income regions, early and accurate diagnosis, which is critical in preventing diseases from progressing to their fatal stages, is not possible. Methods such as polymerase chain reaction (PCR) are often impractical in such regions due to their complexity and high running costs. Loop-mediated isothermal amplification (LAMP) is a promising alternative diagnostic technology that amplifies and detects a specific DNA sequence from a sample. Its features, such as high sensitivity and specificity, affordability, simplicity and versatility, make it an attractive alternative for poorer countries. Moreover, LAMP operates under isothermal conditions, thereby reducing the need for expensive equipment. This review evaluates the applicability of LAMP to be used as an alternative POC diagnostic method for parasitic infections by comparing it with routinely used diagnostic methods. Furthermore, several emerging trends in LAMP technology, such as multiplex LAMP, reverse transcription LAMP, microfluidic chip-incorporated LAMP, digital LAMP, and single nucleotide polymorphism LAMP, are discussed, further illustrating the potential of improving the diagnostic accuracy and affordability of LAMP. The need for cost-effective and accurate diagnostic tools is critical, particularly in regions where parasitic diseases are most prevalent. LAMP represents a viable solution to reduce the burden of parasitic diseases through improved diagnostic capabilities.
Leishmaniasis is a group of neglected tropical diseases (NTDs) caused by protozoa of the genus Leishmania that affect vulnerable populations in tropical and subtropical regions. The disease manifests in cutaneous, mucocu...Leishmaniasis is a group of neglected tropical diseases (NTDs) caused by protozoa of the genus Leishmania that affect vulnerable populations in tropical and subtropical regions. The disease manifests in cutaneous, mucocutaneous, and visceral clinical forms. This major public health disease presents high morbidity, and despite the global impact of leishmaniasis, there are few therapeutic options available and no currently licensed human vaccines. Besides, the available therapeutic agents are associated with high toxicity and treatment failure. These limitations highlight the importance of identifying new therapeutic targets, which will contribute to the development of more effective, safer and shorter treatment options. In this context, surface molecules of Leishmania emerge as attractive therapeutic targets due to their roles in host cell adhesion, immune evasion, and intracellular survival. In addition to their translational potential for drug discovery and vaccine development, these surface molecules are key virulence factors that play central roles in parasite biology and disease pathogenesis. Understanding their structure and function is essential not only for elucidating mechanisms of host-parasite interaction, but also for identifying novel therapeutic and prophylactic strategies. Importantly, molecules such as GP63 (a major surface metalloprotease), LPG (lipophosphoglycan), and KMP-11 (kinetoplastid membrane protein 11) combine essential biological functions with demonstrated immunogenic properties, making them promise as targets for both chemotherapeutic and prophylactic interventions. This review aims to explore the structural and functional characteristics of major surface virulence factors in Leishmania, highlighting their roles in the parasite-host interaction and discussing their translational potential for therapeutic and vaccine development.
The emergence of multidrug resistance in Plasmodium falciparum poses a serious threat to antimalarial treatment, particularly with growing resistance to artemisinin-based combination therapies (ACTs) and partner drugs li...The emergence of multidrug resistance in Plasmodium falciparum poses a serious threat to antimalarial treatment, particularly with growing resistance to artemisinin-based combination therapies (ACTs) and partner drugs like piperaquine. Mutations in key proteins, such as PfCRT (P. falciparum chloroquine resistance transporter) and PfDHFR (P. falciparum dihydrofolate reductase), play a critical role in this resistance. Understanding these molecular mechanisms is essential for the development of effective antimalarial therapies. This study aimed to investigate the structural and functional impact of polymorphisms on drug-target interactions and resistance mechanisms in P. falciparum. Molecular docking and molecular dynamics (MD) simulations were performed to analyze interactions of the mutated PfCRT and PfDHFR proteins with nine antimalarial drugs, including piperaquine. The PfCRT-K76A piperaquine complex strong binding affinity (-9.5 kcal/mol) with moderate structural deviation (0.970 ± 0.202 nm) and greater solvent accessibility (246.01 ± 6.135 nm²), suggesting favourable binding conditions. The PfDHFR-N51I-piperaquine complex showed even stronger binding (-10.8 kcal/mol) but higher structural fluctuation (RMSD: 4.491 ± 1.462 nm) and increased compactness (1.861 ± 0.029 nm), which may reflect restricted ligand accommodation and possible resistance. Overall, the findings provide valuable insights into how PfCRT and PfDHFR mutations contribute to drug resistance and establish a foundation for designing more effective antimalarial strategies. Future research should integrate experimental validation and explore additional resistance-associated mutations to develop targeted therapies for combating multidrug-resistant P. falciparum.
Parasitic diseases caused by Leishmania spp. create considerable health concerns in animals, resulting in a considerable financial impact. They causes a complex infection in equines, affecting weight gain, skin, liver, a...Parasitic diseases caused by Leishmania spp. create considerable health concerns in animals, resulting in a considerable financial impact. They causes a complex infection in equines, affecting weight gain, skin, liver, and spleen. To date, there is a lack of reports on the occurrence of Leishmania in equines in Southern Punjab, Pakistan, highlighting the need for molecular epidemiological surveillance. The current study focused on determining the prevalence of Leishmania in the equine population from District Rahim Yar Khan, Southern Punjab, Pakistan, through amplification of mitochondrial (Cytochrome b) and nuclear (18S rRNA) genes of the parasite. For this purpose, a total of 384 equine - i.e. horses, mules, and donkeys - blood specimens, determined by calculation of the sample size formula, were obtained from District Rahim Yar Khan. The parasite was examined through the Microhematocrit method under the microscope. Leishmania was detected from the buffy coat layer after centrifugation of blood-filled microhematocrit tubes. To detect and characterize Leishmania spp.at the molecular level, DNA extraction from blood samples was carried out using standardized commercial kits, followed by PCR amplification. Information on potential risk factors was gathered through a structured questionnaire. The overall prevalence of Leishmania infection was observed to be 2.1 % via microscopy and 7.3 % and 8.8 % by amplification of the 18S rRNA and Cytochrome b genes using molecular methods. A significantly higher infection percentage was observed in female animals compared to males, and in older and underweight animals compared to younger and healthier ones. Additionally, the infection was non-significantly (P ≥ 0.05) more prevalent in gestating, non-dewormed, symptomatic, and poor body condition animals. Phylogenetic and sequence analyses confirmed that the identified gene sequences clustered within the Leishmania (Leishmania) infantum clade, consistent with strains reported in different animal hosts from various regions. In conclusion, the nuclear gene, i.e., 18S rRNA proved to be a more sensitive molecular marker for detecting Leishmania infection in equines compared to the mitochondrial gene, i.e., Cytochrome b.
Andrade-Silva V, Waldman J, Juliano MA
… +2 more, Tirloni L, da Silva Vaz I
Mol Biochem Parasitol
· 2025 Sep · PMID 40885405
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The cattle tick Rhipicephalus microplus poses a major problem to the livestock industry worldwide, with acaricides resistance presenting an increasing challenge. On other hand, vaccination has been suggested as a better...The cattle tick Rhipicephalus microplus poses a major problem to the livestock industry worldwide, with acaricides resistance presenting an increasing challenge. On other hand, vaccination has been suggested as a better strategy for tick control, and peptide-based vaccines could be developed to target multiple tick antigens. Nevertheless, there are still limitations to the identification of epitopes in tick candidate antigens, as the bioinformatics tools currently available were developed almost exclusively based on mammalian genomes. Therefore, improving the performance of B-cell epitope predictor algorithms is essential to achieve an effective multi-epitope vaccine for tick control. The aim of this study was to reduce costs and increase the efficacy in identifying epitopes in tick antigens. We first evaluated the performance of B-cell epitope predictor algorithms in replicating the results of an in vitro epitope mapping result for the tick salivary serpin RmS-17 as a "benchmark". Then the algorithm with the best performance was employed to predict epitopes for the tick salivary serpin RmS-6, and we screened the candidate epitopes based on predictions that were close to the reactive center loop (RCL), the region of the serpin that interacts with the target protease. Antibodies raised against p1RmS-6 and p3RmS-6 neutralize RmS-6 activity. Using this strategy, we were able to adjust an in silico algorithm predictor based on a Pepscan result to identify epitopes in another serpin. Our strategy offers a cost-effective way to identify neutralizing epitopes in serpins. Furthermore, this strategy can be applied to identify epitopes in serpins and other proteins from other tick species, potentially leading to the development of a peptide-based anti-tick vaccine.
Chemotherapy is a cornerstone in the battle against leishmaniasis, a neglected tropical disease caused by Leishmania parasites that affects millions worldwide. An alarming number of reports are describing treatment failu...Chemotherapy is a cornerstone in the battle against leishmaniasis, a neglected tropical disease caused by Leishmania parasites that affects millions worldwide. An alarming number of reports are describing treatment failure with currently available drugs, thereby explaining the dire need for the discovery of novel compounds, preferably with yet unexplored modes of action. In this respect L. donovani dynamin-1 like protein (LdoDLP1) is of interest as mutations in LdoDLP1 were recently shown to confer resistance to a new antileishmanial compound, suggesting it to be a potential drug target. Through a combination of biochemical, structural, and biophysical methods, we were able to show that wild-type LdoDLP1 has a strong inherent propensity to self-assemble into higher-order oligomers. Guided by structural modeling, a selection of nine point mutations (including resistance markers) were screened for oligomerization behavior to generate self-assembly impaired LdoDLP1 mutants that would occur in solution as dimers and/or tetramers. This led to the identification of a double mutant (G354D/R357S) that exhibits significantly altered and reduced, yet not completely abolished, oligomerization behavior. Further characterization of the LdoDLP1 G354D/R357S double mutant using small-angle X-ray scattering (SAXS) revealed that a fraction of the protein population occurs as a dimer in solution. Additionally, SAXS analysis experimentally confirmed that LdoDLP1, like other dynamin-like proteins, lacks the structurally defined pleckstrin homology (PH) domain of classical dynamins but instead possesses an intrinsically disordered B insert, grouping it among the dynamin-like proteins that play key roles in processes such as mitochondrial fission.
Recently, there has been an increased focus on the development of novel anti-parasitic drugs that exhibit both highly efficacy and low toxicity due to growing concerns associated with the widespread use of such drugs. Na...Recently, there has been an increased focus on the development of novel anti-parasitic drugs that exhibit both highly efficacy and low toxicity due to growing concerns associated with the widespread use of such drugs. Natural products have garnered significant interest owing to their diverse biological activities and minimal adverse effects. In this study, we assessed the anti-Eimeria tenella activity of four plant compounds belonging to the Lamiaceae family, namely Perillyl alcohol, Carvone, Menthone and Perilla aldehyde. Our in vitro experiments demonstrated that all four compounds, particularly Perillyl alcohol, exhibited potent inhibition against sporulation formation of E. tenella oocyst. Furthermore, our in vivo tests revealed that treatment with these four compounds at a dose of 200 mg/kg significantly reduced oocyst shedding as well as cecal lesions and weight loss caused by E. tenella infection, thereby demonstrating moderate anti-E. tenella activity. Notably, Perillyl alcohol displayed the highest efficacy against E. tenella with an anticoccidial index (ACI) value of 161.4. In summary, our findings indicate that these four compounds derived from the Lamiaceae family exhibit anti-E. tenella activity both in vitro and in vivo, with Perillyl alcohol displaying particularly robust inhibitory effects on E. tenella. It is worthy of further investigation to explore its mechanism of action and potential therapeutic applications.
Ovine theileriosis is a disease caused by the genus Theileria (e.g., T. ovis, T. lestoquardi), preventing the sheep farming industry from developing, particularly in regions reliant on sheep for milk, meat, and associate...Ovine theileriosis is a disease caused by the genus Theileria (e.g., T. ovis, T. lestoquardi), preventing the sheep farming industry from developing, particularly in regions reliant on sheep for milk, meat, and associated economic benefits. However, there is limited information available on the epidemiological data and genetic diversity of T. ovis in Xinjiang. This study was conducted in May 2024 to investigate the molecular prevalence of T. ovis in sheep from five counties (Shaya, Wensu, Aketao, Keping, Awati) in Xinjiang. A total of 357 blood samples were screened for the presence of Theileria DNA through the amplification of the 18S rRNA gene using PCR, the genetic diversity among the chosen T. ovis sequences from geographical regions (including sequences in this study) was subsequently analyzed. BLAST analysis confirmed that the detected Theileria pathogen was T. ovis. Statistical results showed that the infection rate of T. ovis in sheep was 44.5 % (159/357). The highest infection rate was observed in Awati County, while the lowest was recorded in Shaya County. The prevalence exhibited significant variation among the sampling sites (χ² = 115.3, p < 0.05). To characterize the phylogenetic relationships within the detected Theileria populations, the sequenced T. ovis isolates were analyzed and found to be 96.6-99.8 % similar, showing a high degree of similarity to isolates from Turkey. Haplotype analysis further demonstrated that H1 constitutes the core haplotype (including sequences from Turkey, Iraq and Saudi Arabia), surrounded by derivative haplotype. To further investigate these haplotype distributions, population structure analysis revealed distinct genetic diversity patterns among groups, showing that genetic groups G1 and G4 had high haplotype diversity (Hd) but low nucleotide diversity (Pi), whereas G2 and G3 had low Hd and high Pi. In addition, Tajima's D<0 in all four T. ovis populations. These biological and genetic indices suggest that these populations are possibly undergoing expansion. Our results suggest that the protozoan parasitizing local sheep is T. ovis. Moreover, the local population of T. ovis is as rich in genetic diversity and population expansion as other populations in different geographical locations.
Otodectes cynotis (ear mite), the primary etiological agent of feline otitis externa, represents a significant veterinary concern due to its high prevalence and treatment challenges. Glutathione S-transferase (GST), a de...Otodectes cynotis (ear mite), the primary etiological agent of feline otitis externa, represents a significant veterinary concern due to its high prevalence and treatment challenges. Glutathione S-transferase (GST), a detoxifying and immunogenic enzyme in various parasites, is a potential molecular target for vaccine development. In this study, we cloned and heterologously expressed the GST gene from O. cynotis, confirmed its recombinant protein activity using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate, and determined its optimal enzymatic conditions (pH 8, 30 °C). Bioinformatic analysis revealed high sequence conservation with arthropod homologs, predicted functional domains, and identified several immunogenic B- and T-cell epitopes. Molecular docking with ethacrynic acid indicated stable binding, suggesting GST as a potential drug target. This study presents the first functional and immunogenic characterization of O. cynotis GST, suggesting its critical role in oxidative stress mitigation and drug detoxification, and supporting its potential as an anti-mite vaccine candidate.
Copper plays an essential role in organisms as a catalytic co-factor for key enzymes like cytochrome c oxidase. Copper importation, distribution and secretion is carried out by copper transport and copper-binding protein...Copper plays an essential role in organisms as a catalytic co-factor for key enzymes like cytochrome c oxidase. Copper importation, distribution and secretion is carried out by copper transport and copper-binding proteins known as copper chaperones. Cox17 is a chaperone that conveys copper to Cox11 and Sco1 for metalation of the Cu and Cu of Cox1 and Cox2 respectively in eukaryotes. Cox17 from Trypanosoma brucei brucei and T. congolense were recombinantly expressed and affinity purified as MBP-fusion proteins. An ascorbic acid oxidation assay, a BCA-release assay and an in vivo growth inhibition assay confirmed the presence of copper bound to the proteins. Trypanosomal Cox17 and other copper-binding proteins are expressed at higher levels in the insect procyclic stage where cytochrome c oxidase is active, compared to the bovine bloodstream forms. In silico docking models suggests possible interaction partners for Cox17.
Calcium/calmodulin-dependent protein kinase II (CaMKII) performs diverse essential functions through integrating a range of calcium signals. In Schistosoma, two Calmodulin (CaM) genes are characterized. CaMKII exhibits d...Calcium/calmodulin-dependent protein kinase II (CaMKII) performs diverse essential functions through integrating a range of calcium signals. In Schistosoma, two Calmodulin (CaM) genes are characterized. CaMKII exhibits distinct expression patterns across the developmental stages of the parasite. Its significance lies in sustaining Schistosoma survival and maintaining calcium homeostasis. As it is a calcium sensing protein, its function is closely related to the efficacy of praziquantel, the mainstay drug against schistosomiasis. The relationship between CaMKII and praziquantel involves several potential factors. Praziquantel induces an increased calcium influx into Schistosoma that binds CaM and activates CaMKII, which in turn mitigates the effect of the drug and potentially contributes to praziquantel resistance in several ways. By maintaining calcium homeostasis, CaMKII opposes the surge in calcium influx induced by praziquantel. It modulates voltage-gated calcium channels and reduces calcium influx. It also inhibits ryanodine receptors and inositol triphosphate receptors, thus preventing the release of calcium from the sarcoplasmic/endoplasmic reticulum. CaMKII activates nuclear factor-κB and subsequently activates sarco/endoplasmic reticulum calcium-ATPase (SERCA), which increases calcium uptake into the sarcoplasmic/endoplasmic reticulum and decreases cytosolic calcium. Nuclear factor-κB, activated by CaMKII may lead to up-regulation of P-glycoprotein, which facilitates praziquantel efflux. CaMKII also activates calcineurin that inhibits SERCA. Given its pivotal role in Schistosoma homeostasis and survival, CaMKII emerges as a promising target for novel anthelmintic therapies, and its modulation might enhance the efficacy of praziquantel.
The present study investigated for the first time the influence of exposure time (24 or 48 h) of Biomphalaria glabrata (Gastropoda: Pulmonata) to Heterorhabditis bacteriophora (Rhabditida: Heterorhabditidae), strain HP88...The present study investigated for the first time the influence of exposure time (24 or 48 h) of Biomphalaria glabrata (Gastropoda: Pulmonata) to Heterorhabditis bacteriophora (Rhabditida: Heterorhabditidae), strain HP88, on some physiological and reproductive parameters of the host mollusk. Throughout the experiment, intense glycogenolysis was observed in both exposed groups, which was more accentuated in the digestive gland. This change was accompanied by a significant increase in the free glucose content in the exposed snails, indicating that H. bacteriophora infection induces the breakdown of host glycemic homeostasis. In parallel, significant variations in lactate dehydrogenase activity in the hemolymph of B. glabrata exposed to entomopathogenic nematodes were observed, confirming the transition from aerobic to anaerobic metabolism in the hosts. This physiological scenario contributed to the establishment of the parasitic castration process in this interface, compromising the reproductive performance of host snails, suggesting the use of H. bacteriophora HP88 as a potential alternative for control of B. glabrata.
Leishmania species are intracellular protozoans responsible for causing both cutaneous and visceral infections. In recent years, the prevalence of leishmaniasis, a systemic and chronic disease, has been on the rise. Comp...Leishmania species are intracellular protozoans responsible for causing both cutaneous and visceral infections. In recent years, the prevalence of leishmaniasis, a systemic and chronic disease, has been on the rise. Complement pathway mechanisms, part of the immune response of host organisms against Leishmania species, have not been fully revealed in leishmaniasis, which is very important for public health. This study aimed to explore the role of the complement system, an integral part of the immune response to Leishmania infections, in gerbil (Meriones unguiculatus) models of cutaneous leishmaniasis. This was achieved by assessing the expression levels of complement system genes (MBL-1, MBL-2, C2, and C3) and quantifying the protein levels of MBL-1, C2, and C3. Additionally, the study aimed to conduct biochemical tests, specifically measuring GSH and MDA levels, to detect oxidative stress in response to infection in gerbils. Finally, hematological analyses were performed to evaluate leukocyte counts in the blood. The expression of complement system genes and some complement system proteins were significantly increased in infected gerbils. Oxidative stress was evident, as indicated by reduced GSH levels and increased MDA levels. Additionally, a significant rise in leukocyte counts was observed as a consequence of the infection. The study concluded that complement system pathways are activated in cutaneous leishmaniasis infections. It was also determined that a thorough evaluation of genomic, proteomic, and immunopathological mechanisms is essential for understanding the pathogenesis of the disease.
The causative agent of giardiasis in human and animals is the amitochondriate Giardia lamblia. We observed that exposing Giardia trophozoites to MTZ led to an increase in lipid peroxidation compared to the control group,...The causative agent of giardiasis in human and animals is the amitochondriate Giardia lamblia. We observed that exposing Giardia trophozoites to MTZ led to an increase in lipid peroxidation compared to the control group, which was expressed in terms of menadione production as it is the marker for lipo-peroxidation. Oxidative stress generated by reactive nitrogen species and peroxidation of membrane phospholipids are positively correlated with the enhanced PLA2 activity in several organisms to produce arachidonic acid (AA). Our data suggested Giardia produces a unique 56 kDa dimeric enzyme called Phospholipase B (gPLB) in contrast to higher eukaryotes which was responsible for the production of intracellular free AA. This free AA either reacylates to the cell membrane or deacylates to further produce prostaglandins. In normal un-induced controlled trophozoites the membrane reacylation process was dominant due the higher level of acyle CoA synthase (ACS) expression over the time. However, under the oxidative stressed condition the intracellular ACS expression was down regulated. This led to the increase in deacylation process. When AA deacylation becomes dominant over AA reacylation in cells, the free AA accumulates intracellularly. One of the lipid autacoids, derived from AA is prostaglandin2 (PGE2). Oxidative stress generated by reactive nitrogen species in trophozoites increased the PGE2 production via prostaglandin synthase over the time with respect to the controlled one.
This study investigates the prevalence, severity, and impacts of parasitic infestations in Clarias gariepinus. Additionally, the study assesses the detrimental impacts of parasite infestation on the health condition of a...This study investigates the prevalence, severity, and impacts of parasitic infestations in Clarias gariepinus. Additionally, the study assesses the detrimental impacts of parasite infestation on the health condition of affected catfish, focusing on biochemical and histopathological alterations. A total of 160 fish were sampled from local markets. Parasitological examinations involved the dissection of key organs from each fish. The organs were processed and examined microscopically for parasites identified based on morphometric characteristics. Parasitological indices such as prevalence, mean intensity, and abundance were calculated. Fish blood and liver samples were collected to assess hematological and biochemical parameters. Microscopic and ultrastructural examinations identified the gills and liver as highly infected organs, so they were utilized for transmission electron microscopy (TEM). Analysis of catfish tissues unveiled the existence of Cyathocotylid sp. and Prohemistomum vivax, across all organs with dominance noted in the liver, emphasizing their pathogenic significance and notable ability to invade and establish within multiple organs or the immunocompromised response of the host. Meanwhile, Centrocestus formosanus and Quadriacanthus aegyptiacus were exclusively detected in the gills, with an overall parasitic infection rate of 60 %. The present study is one of the few studies documenting Centrocestus sp. in catfish which reflects its ability to spread in new hosts and environments. A novel morphological dimension was recorded for the recovered metacercariae. The hematological, along with the identified lesions from light histological and TEM examinations in heavily infected catfish, indicate the detrimental impact of parasite infiltration on fish health status. Besides the biochemical biomarkers were significantly (p ≤ 0.05) affected by increasing the degree of infection. This study underscores the profound influence of parasitic infestations on the health of C. gariepinus, emphasizing the urgent need for effective management strategies in aquaculture to mitigate these effects, the spread of new pathogens, and ensure the sustainability and productivity of catfish farming. By integrating parasitological, morphological, histopathological, and biochemical analyses, this research provides valuable insights that contribute to better health management strategies in aquaculture and a deeper understanding of parasite biology.
In this work the relationship between Schistosoma mansoni (Sm) and the induction and progression of colorectal cancer (CRC) is examined. Various clinical studies reviewed here yield inconsistent results, with some report...In this work the relationship between Schistosoma mansoni (Sm) and the induction and progression of colorectal cancer (CRC) is examined. Various clinical studies reviewed here yield inconsistent results, with some reporting no association between Sm infection and CRC and others suggesting a probable to strong association. Here we propose a number of plausible mechanisms whereby Sm infection might contribute to CRC induction and/or progression. These factors are (1) chronic inflammation, (2) exposure to parasite linked antigens and genotoxic products, especially soluble egg antigens (SEAs) and (3) alteration of the intestinal microbiota. These factors probably predispose humans towards CRC and can help in CRC progression however only widespread epidemiological, clinical and pathological studies can firmly establish their role or a complete lack of it.
Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affectin...Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy. The heterocyclic ring oxadiazole has been documented in the literature to possess various biological activities, including leishmanicidal properties, thus positioning it as a potential candidate for further investigation. This study aims to evaluate the in vitro leishmanicidal activity of an oxadiazole compound (2i), explore its mechanism of action through enzymatic inhibition and molecular docking, assess its antioxidant activity, and conduct an in silico pharmacokinetic prediction. Pharmacokinetic predictions via ADME/TOX modeling revealed that the 2i molecule exhibits good intestinal absorption (92 %), is water-insoluble (-4 log.mol/L) and demonstrates high permeability in Caco-2 cells (1.35 log.Papp10-6cm/s), suggesting potential for oral administration. Metabolic studies indicated that oxadiazole 2i is an inhibitor of cytochrome P450 enzymes CYP1A2 and CYP2C19, necessitating further evaluation of potential drug interactions. Additionally, it did not exhibit hepatotoxicity or cardiotoxicity; however, it demonstrated mutagenic potential in the salmonella reverse mutation test (AMES), which is a genetic method that detects mutagenic chemical agents, thus justifying more complex confirmatory studies. In vitro assays showed that oxadiazole 2i has DPPH (2,2-diphenyl-1-picrylhydrazyl) radical reducing activity, indicating potential antioxidant properties with an IC of 12.10 µg/mL. Concerning its leishmanicidal mechanism of action, molecular docking simulations at the active site of acetylcholinesterase demonstrated that the 2i molecule had superior binding energy values compared to the reference drug physostigmine (-7.39 kcal/mol versus -6.66 kcal/mol, respectively). However, the pharmacophore map revealed that physostigmine had more molecular interactions than oxadiazole 2i. In acetylcholinesterase inhibition assays, the 2i molecule exhibited significant inhibitory activity with an IC of 11.91 µg/mL, suggesting a mechanism of action that compromises the parasitic membrane. Moreover, the 2i molecule demonstrated significant leishmanicidal activity against L. infantum with an IC of 30.86 μM. Cytotoxicity assays on RAW 264.7 macrophages revealed a high CC value of 485.5 µM and a selectivity index (SI) of 17.86. Based on these findings, oxadiazole 2i emerges as a promising candidate for further study, offering prospects for more affordable, selective, and less toxic leishmanicidal agents.
This study investigated the effect of dandelion (Taraxacum officinale) leaf aqueous extract (DLE) on the immunological response of mice following infection with Schistosoma mansoni. Mice (in groups of 7) were first exper...This study investigated the effect of dandelion (Taraxacum officinale) leaf aqueous extract (DLE) on the immunological response of mice following infection with Schistosoma mansoni. Mice (in groups of 7) were first experimentally infected with S. mansoni and, 6 weeks later, were treated with praziquantel (PZQ) and/or DLE. Control mice were uninfected. In contrast to the untreated group, animals given PZQ and/or DLE exhibited an enhanced immunological response, as indicated by increased serum IFNγ, TNFα, IL4 and IL10 levels, increased numbers of CD4 + and CD25 + cells in blood and spleen and altered expression of apoptosis-related genes (low Bax and caspase3 and high Bcl2) in the spleen. DLE treatment had a significantly bigger impact in all these parameters compared with PZQ alone and combined DLE/PZQ treatment have the largest effect. While DLE treatment alone significantly decreased parasite burden, it did not improve upon the greater protective effect of PZQ, even when given in combination.