Search

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondiis invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk populations exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

BACKGROUND: Timely molecular surveillance of Plasmodium falciparum kelch 13 (k13) gene mutations is essential for monitoring the emergence and stemming the spread of artemisinin resistance. Widespread artemisinin resistance, as observed in Southeast Asia, would reverse significant gains that have been made against the malaria burden in Africa. The purpose of this study was to assess the prevalence of k13 polymorphisms in western Kenya and Ethiopia at sites representing varying transmission intensities between 2018 and 2022. METHODS: Dried blood spot samples collected through ongoing passive surveillance and malaria epidemiological studies, respectively, were investigated. The k13 gene was genotyped in P. falciparum isolates with high parasitaemia: 775 isolates from four sites in western Kenya (Homa Bay, Kakamega, Kisii, and Kombewa) and 319 isolates from five sites across Ethiopia (Arjo, Awash, Gambella, Dire Dawa, and Semera). DNA sequence variation and neutrality were analysed within each study site where mutant alleles were detected. RESULTS: Sixteen Kelch13 haplotypes were detected in this study. Prevalence of nonsynonymous k13 mutations was low in both western Kenya (25/783, 3.19%) and Ethiopia (5/319, 1.57%) across the study period. Two WHO-validated mutations were detected: A675V in three isolates from Kenya and R622I in four isolates from Ethiopia. Seventeen samples from Kenya carried synonymous mutations (2.17%). No synonymous mutations were detected in Ethiopia. Genetic variation analyses and tests of neutrality further suggest an excess of low frequency polymorphisms in each study site. Fu and Lis F test statistic in Semera was 0.48 (P > 0.05), suggesting potential population selection of R622I, which appeared at a relatively high frequency (3/22, 13.04%). CONCLUSIONS: This study presents an updated report on the low frequency of k13 mutations in western Kenya and Ethiopia. The WHO-validated R622I mutation, which has previously only been reported along the north-west border of Ethiopia, appeared in four isolates collected from eastern Ethiopia. The rapid expansion of R622I across Ethiopia signals the need for enhanced monitoring of the spread of drug-resistant P. falciparum parasites in East Africa. Although ACT remains currently efficacious in the study areas, continued surveillance is necessary to detect early indicators of artemisinin partial resistance.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

The intestinal parasites Giardia lamblia and Entamoeba histolytica are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%-40% of cases. Potential resistance of E. histolytica to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against E. histolytica and G. lamblia trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of G. lamblia. G. lamblia and E. histolytica cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of E. histolytica trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg/kg for 3 days reduced G. lamblia infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.

This 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. [ABSTRACT FROM AUTHOR]

Green synthesized silver nanoparticles (AgNPs) have received lots of attention due to being used as potential therapeutic agents. For the first time, this research investigated the biosynthesis of silver nanoparticles using the extract of Daphne mucronata seeds, which are rich in phenolic and polyphenolic substances and evaluated their antibacterial, antifungal, and scavenging activities. The process of nanoparticle (NPs) preparation was confirmed using UV–vis spectroscopy with an absorption peak at a wavelength of 440 nm. Dynamic light scattering (DLS) was used to determine the particles' distribution. Fourier‐transform infrared spectroscopy (FTIR) validated the functional groups contributing to the reduction of Ag+ to Ag. Moreover, X‐ray diffraction analysis (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) approved the crystalline nature and spherical shape of the particles with mean and standard deviation of particle size to be 60.25 and 24.88 nm, respectively. The antibacterial, antifungal, and scolicidal activities of AgNPs were studied using disc diffusion against four standard bacteria species and microdilution methods for four Candida strains. The greatest effect of AgNPs with the highest concentration (80 µg/mL) was observed on Staphylococcus aureus (22.26 mm) and the lowest on Pseudomonas aeruginosa (19.07 mm). In the case of Candida fungus, the highest effect of AgNPs was reported for Candida krusei (7.93 µg/mL) and the lowest for Candida albicans (63.49 µg/mL). Also, these nanoparticles were able to register 100% lethality on the Echinococcus granulosus parasite in 15 min at a concentration (80 µg/mL). Therefore, the production of AgNPs as a renewable and cheap material can be effective after performing all the necessary tests as antibacterial, antifungal and antiparasitic agents with the least side effects in biomedical and pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

Fish-borne zoonotic trematodes (FBZTs) pose significant health risks and economic challenges worldwide. This study investigated the prevalence of encysted metacercariae (EMCs) in Nile tilapia (Oreochromis niloticus) from two Egyptian governorates and evaluated the antiparasitic efficacy of chitosan, silver, and selenium nanoparticles against these parasites. A cross-sectional analysis of 453 O. niloticus specimens revealed an overall EMC prevalence of 40.8%, with infection rates of 34.11% in Giza and 49.5% in Dakahlia. Clinostomid and Prohemistomid metacercariae were the most common, with mixed infections observed. Transmission electron microscopy characterized the synthesized nanoparticles, showing average diameters of 9.6–18.7 nm for chitosan, 13.2–19.8 nm for selenium, and 11.7–15.1 nm for silver nanoparticles. In vitro antiparasitic assays demonstrated varying efficacies among the nanoparticles. Against Clinostomum spp. metacercariae, chitosan nanoparticles showed the highest potency, achieving LC50 at 66 μg/ml after 30 min and LC90 at 100 μg/ml after 120 min. For Prohemistomum vivax EMCs, chitosan nanoparticles exhibited superior efficacy, achieving LC50 at 8 μg/ml after 1 h and LC90 at 16 μg/ml after 2 h. Silver and selenium nanoparticles showed lower efficacy for both parasite species. Scanning electron microscopy revealed significant ultrastructural damage to the parasite tegument following nanoparticle exposure, including disappearance of transverse ridges, integument shrinkage, and formation of blebs. This study provided valuable insights into the prevalence of FBZTs in Egyptian Nile tilapia and demonstrated the potential of nanoparticles, particularly chitosan, as effective antiparasitic agents. These findings pave the way for developing novel, targeted strategies to control fish-borne zoonotic trematodes, potentially reducing their impact on public health and aquaculture economies. [ABSTRACT FROM AUTHOR]

Background: In Venezuela, the predominant vaccines administered are BBIBP-CorV and Gam-COVID-Vac. Despite robust evidence from randomized clinical trials validating the effectiveness of COVID-19 vaccines in mitigating hospitalization and mortality, there is still a lack of post-authorization safety studies conducted within this demographic population. Methods: A prospective observational study from October 5, 2021 to March 31, 2022 encompassed COVID-19 vaccinated and unvaccinated patients from four sentinel hospitals in Venezuela. Patient lethality was predicted using Charlson Comorbidity index. Clinical outcomes were assessed through WHO's COVID-19 Clinical Progression Scale. Results: Out of the 175 patients assessed, 85 (48.6%) were vaccinated. The median Charlson Comorbidity index was 3 points, with no statistically significant differences observed between the groups (p = 0.2). A total of 50 (28.6%) patients died during the study period, with higher proportion of deaths in unvaccinated patients (35.6% vs. 21.2%, p = 0.035). Advanced age (OR = 1.043, 95% CI = 1.015–1.071, p = 0.002) was associated with increased death risk, whereas vaccination against COVID-19 (OR = 0.428, 95% CI = 0.185–0.99, p = 0.047), high oxygen saturation (OR = 0.964, 95% CI = 0.934–0.995, p = 0.024), and enoxaparin administration (OR = 0.292, 95% CI = 0.093–0.917, p = 0.035) were associated with decreased death risk. Conclusion: During the third and fourth waves of the pandemic, COVID-19 vaccination was associated with a 57% reduction in lethality among patients in four public hospitals in Venezuela. Key summary points: Less than half (48.6%) of the patients were vaccinated against SARS-CoV-2. At least one out of four patients died during the study period, mainly in the unvaccinated group. Advanced age was associated with a higher risk of death. Vaccination against COVID-19, high oxygen, and enoxaparin administration were factors associated with a lower risk of death. [ABSTRACT FROM AUTHOR]

Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide. This fact impairs technological advancements and investments in innovative therapeutic approaches, so that commonly available drugs are still associated with low therapeutic rates and significant side effects. Pentavalent antimonials, such as Pentostan® and Glucantime®, were established as chemotherapeutic agents since the 1940s, being the first line of treatment for leishmaniasis; however, 60% of cases of leishmaniasis are resistant to pentavalent antimonials. Thus, the search for more effective therapies and new therapeutic agents with potential leishmanicidal activity is still in-demand. In this review, an overview about the disease and its pathophysiology is given, discussing the current state-of-the-art of the standard treatments and new alternatives based on drug delivery approaches, enhancing the need for more effective pharmaceutical treatments. [ABSTRACT FROM AUTHOR]

Echinococcosis represents a major public health issue and continues to be endemic in various regions around the world. Hydatid cysts are commonly located in the liver (primary site), followed by the lungs (secondary site). However, they are also found in less typical organs such as the spleen, kidneys, peritoneum, retroperitoneum, pancreas, gallbladder, and various other organs, as well as in striate muscles. Hydatid cysts involving the psoas muscle are rare, and in the past five years, only a few articles have addressed this condition due to its low incidence. Symptoms can be quite vague, and serological testing might return negative, making imaging studies crucial for an accurate diagnosis. Treatment options involve surgery alongside antiparasitic agents. Despite having a low mortality rate, the recurrence of hydatid disease remains high. This paper aims to provide new clinical data through our case presentation, while also offering a review of the cases of hydatid cysts involving the psoas muscle that have been published over the past five years. [ABSTRACT FROM AUTHOR]

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient‐friendly orodispersible tablet formulation designed for pediatric use (CHILD‐IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD‐IVITAB, 16 healthy adults were enrolled in a phase I, single‐center, open‐label, randomized, 2‐period, crossover, single‐dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD‐IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD‐IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD‐IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for Cmax, AUC 0‐∞, and AUC0‐last, which were 1.52 [90% CI: 1.13‐2.04], 1.27 [0.99‐1.62], and 1.29 [1.00‐1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD‐IVITAB formulation, with a median Tmax at 3.0 h [range 2.0‐4.0 h] versus 4.0 h [range 2.0‐5.0 h] with STROMECTOL (P =.004). With CHILD‐IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD‐IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient‐friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg. [ABSTRACT FROM AUTHOR]

Problem: Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania and has a high prevalence and impact on global health. Currently, the available drugs for its treatment have drawbacks, such as high toxicity, resistance of the parasite, and high cost. Therefore, the search for new, more effective, and safe drugs is a priority. The effectiveness of an anti-leishmanial drug is analyzed through in vitro studies in which a technician manually counts the intracellular form of the parasite (amastigote) within macrophages, which is slow, laborious, and prone to errors. Objective(s): To develop a computational system that facilitates the detection and counting of amastigotes in microscopy images obtained from in vitro studies using image processing techniques. Methodology: Segmentation of objects in the microscope image that might be Leishmania amastigotes was performed using the multilevel Otsu method on the saturation component of the hue, saturation, and intensity color model. In addition, morphological operations and the watershed transform combined with the weighted external distance transform were used to separate clustered objects. Then positive (amastigote) objects were detected (and consequently counted) using a classifier algorithm, the selection of which as well as the definition of the features to be used were also part of this research. MATLAB was used for the development of the system. Results and discussion: The results were evaluated in terms of sensitivity, precision, and the F-measure and suggested a favorable effectiveness of the proposed method. Conclusions: This system can help researchers by allowing large volumes of images of amastigotes to be counted using an automatic image analysis technique. [ABSTRACT FROM AUTHOR]

Antibiotics can be introduced from aquaculture facilities into marine sediments, where they may affect benthic communities and generate antimicrobial resistance (AMR). Antibiotics can be used in tandem with antiparasitics, and the effects of their combined usage could affect AMR patterns and transmit antibiotic resistance genes. This study compiles patterns of antibiotic and antiparasitic drug usage from 2016 to 2021 in British Columbia, New Brunswick, Newfoundland and Labrador, and Nova Scotia (Canada) and compares them internationally. There is an overall reduction in rates of antibiotic use per fish produced in Canadian aquaculture sites from 2016 to 2021. Compared to other salmon-producing countries, Canadian antibiotic rates per tonne of fish are lower than in Chile, but higher, on average, than in Norway and Scotland. Florfenicol (FLO) and oxytetracycline (OTC) are the prevalent antibiotics used in most salmon-producing countries, including Canada. We also note that <30% of sites used two drugs per year and <18% of sites used three drugs, with most of these sites using one antibiotic and one antiparasitic. There is an increase in FLO and a decrease use in OTC use in Canada, which could be positive environmentally considering FLO's lower dose and environmental persistence. The east and west coasts show comparable antibiotic rates, with an average rate of 78 mg/kg in BC and 76 mg/kg in the Atlantic provinces; however, they have differences in the type of antibiotic (average use of OTC: BC 38 mg/kg vs. Atlantic 214 mg/kg; average use of FLO: BC 40 mg/kg vs. Atlantic 10 mg/kg). Other distinctions between coasts include variation in the timing of treatments, with seasonal use in the Atlantic provinces (May–November) and year-round use in BC. This pattern is likely influenced by differences in water temperature and, subsequently, potential susceptibility to aquatic diseases. Disease prevalence and veterinarian choice/preferred treatments are factors that, we hypothesize, may impact treatment choice; however, additional information is required to adequately comment on this point. This data compilation includes spatial descriptions that could be used for area prioritization in future studies. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a tropical infectious disease caused by Leishmania parasites. The disease can be spread by the bite of an infected sand fly. Currently, five chemotherapeutic drugs are available in leishmaniasis treatment. However, these drugs exhibit toxicity and serious adverse effects on infected individuals, necessitating alternative treatment strategies. One such strategy involves using combinations of existing antileishmanial drugs. In this study, we evaluated the interaction between artesunate (AS) and three antileishmanial drugs—amphotericin B (AmB), miltefosine (MF), and paromomycin (PM) against Leishmania infantum. This evaluation marks the first time such an assessment has been conducted. The Chou–Talalay combination index method was employed to analyze the drug interaction. The findings revealed that the interaction between AS and AmB ranged from antagonistic to synergistic, while the interaction between AS and MF showed moderate to strong synergism. In contrast, the interaction between AS and PM resulted in an antagonistic interaction, which differs from the combinations with AmB or MF. This study provides valuable insights for developing novel drug regimens for leishmaniasis treatment, emphasizing the potential of AS and its combination with existing antileishmanial drugs. Further research is necessary to optimize drug combinations and minimize adverse effects, leading to more effective therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Antibiotics are drugs that target and destroy bacteria, and they are hailed as one of the most amazing medical breakthroughs of the 20th century. They have completely changed how we treat infections and have saved countless lives. But their usefulness is not limited to just medicine; they have also been used for many years in sectors like farming to prevent infections in animals, especially in less wealthy countries. Antimicrobial resistance (AMR) is the ability of microorganisms such as bacteria, viruses, fungi, and parasites to resist the effects of antimicrobial agents, like antibiotics, antivirals, antifungals, and antiparasitics, that were once effective in treating infections caused by these organisms. AMR presents an intricate challenge that endangers the health of both humans and animals, as well as the global economy, and the security of nations and the world at large. Because resistant bacteria are swiftly appearing and spreading among humans, animals, and the environment worldwide, AMR is acknowledged as a challenge within the framework of One Health. The One Health approach involves cooperation among various fields to attain the best possible health outcomes for humans, animals, and the environment. It acknowledges the interconnectedness of human, animal, and environmental health. AMR is not merely a scientific or medical issue; it is a societal challenge that demands collective action and awareness. In the intricate tapestry of society, every thread contributes to the fabric of AMR, and every individual holds a stake in its resolution. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by the protozoan Trypanosoma cruzi, represents an important and worldwide public health issue, particularly in Latin America. Limitations of conventional treatment with benznidazole and nifurtimox underscore the urgent need for new therapeutic strategies for this disease. Schinus molle, a tree used in traditional medicine for various ailments, has demonstrated promising antiparasitic activity. The in vitro anti-T. cruzi activity of Schinus molle crude methanol extract, partitions, and fractions, as well as their cytotoxicity in Vero cells and Artemia salina, and hemolytic activity in human erythrocytes were assessed. Most of the extracts possessed anti-T. cruzi effects, with Sm-CF3 being the fraction with the highest activity (IC50 = 19 µg/mL; SI = 6.8). Gas chromatography–mass spectrometry analysis identified 20 compounds, with fatty acyls comprising the predominant chemical class (55%). We also identified the antiparasitic compounds cis-5,8,11,14,17-eicosapentaenoic acid and trans-Z-α-bisabolene epoxide, suggesting their potential contribution to the observed anti-T. cruzi activity. In conclusion, our findings support the therapeutic potential of S. molle as a source of novel antiparasitic agents against T. cruzi. [ABSTRACT FROM AUTHOR]

Demodex blepharitis, a chronic lid margin disease, is caused by an infestation of Demodex mites, the most common ectoparasites in human skin and eyelids. Lotilaner ophthalmic solution, 0.25% (Xdemvy, Tarsus Pharmaceuticals), is the first therapy approved to treat Demodex blepharitis. This narrative review characterizes lotilaner ophthalmic solution, 0.25%, and describes its efficacy, safety, and tolerability. The safety and efficacy of lotilaner ophthalmic solution, 0.25%, for treating Demodex blepharitis was evaluated in four phase 2 and two phase 3 trials. The data of 980 patients included in these phase 2 and 3 clinical trials revealed that the proportion of eyes with a clinically meaningful reduction to 10 or fewer collarettes (the cylindrical, waxy debris found at the base of the eyelashes) ranged from 81 to 93%. The mite eradication rate confirmed by a microscopy of epilated lashes ranged from 52 to 78%. No serious treatment-related adverse events were reported in any of these clinical studies. As high as 92% of the patients receiving lotilaner eyedrops in the phase 3 trials found it to be neutral to very comfortable. Given the positive safety and efficacy outcomes, the drug is likely to become the standard of care in the treatment of Demodex blepharitis. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19. [ABSTRACT FROM AUTHOR]

Due to the limitations of Chagas disease therapy, microalgae can be promising in the search of new trypanocidal compounds, since these organisms produce bioactive compounds with large pharmaceutical applications, including antiparasitic effects. In this work, trypanocidal activity of aqueous extract of Tetradesmus obliquus and, for the first time, aqueous extract of Chlorella vulgaris, were evaluated against trypomastigote forms of Trypanosoma cruzi. In addition, cytotoxic activity in Vero cells was evaluated. Our results showed that C. vulgaris and T. obliquus present trypanocidal activity (IC50 = 32.9 µg ml−1 and 36.4 µg ml−1, respectively), however, C. vulgaris did not present cytotoxic effects in Vero cells (CC50 > 600 µg ml−1) and displayed a higher selectivity against trypomastigotes forms of T. cruzi (SI > 18). Thus, microalgae extracts, such as aqueous extract of C. vulgaris, are promising potential candidates for the development of natural antichagasic drugs. [ABSTRACT FROM AUTHOR]

The growing global threat of antimicrobial resistance endangers both human and animal life, necessitating the urgent discovery of novel antimicrobial solutions. Medicinal plants hold promise as sources of potential antimicrobial compounds. In this study, we investigated the phytochemical constituents and microbicidal capabilities of the ethanolic extract from Nigella sativa (black seed). Gas chromatography analysis (GC) identified 11 compounds, among them thymoquinone, and thymol, contributing to antimicrobial and antioxidant properties. Antimicrobial assays demonstrated notable inhibition zones against broad spectra of bacteria, including Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi, Staphylococcus aureus, Enterobacter, and Bacillus subtilis, along with potent antifungal activity against Aspergillus niger, Penicillium, and Candida albicans. Notably, when combined with antibiotics, the extract displayed exceptional synergistic antimicrobial efficacy. The black seed extract demonstrated membrane-damaging activity and disrupted virulence factors that protect microbes from antimicrobial agents, including the formation of bacterial biofilm and protease secretion. Thymoquinone, the primary active constituent of the extract, exhibited similar antimicrobial and ant virulence properties. In silico analysis targeting key regulators of quorum sensing and biofilm formation in P. aeruginosa, such as RhlG, LasR, and PqsR, showed a remarkable affinity of thymol and thymoquinone for these targets. Moreover, the N. sativa extract exhibited dose-dependent cytotoxicity against both the promastigote and amastigote forms of Leishmania tropica parasites, hinting at potential antiparasitic activity. In addition to its antimicrobial properties, the extract displayed potential antioxidant activity at a concentration of 400 μg/mL. [ABSTRACT FROM AUTHOR]

In current study, anti-parasitic properties of Nicotiana tabacum leaves (N. tabacum L.) and their traditional use in ethno-veterinary therapy were investigated using both in-vitro and in-vivo approaches. Crude aqueous extracts (CAE) of N. tabacum L. were used to evaluate in-vitro antiparasitic effect of Haemonchus (H.) placei that had been directly retrieved from the abomasum of cows. The nematodes' death or paralysis within three hours subsequent to being exposed to different quantities 25, 50 and 100 mg/ml of CAE proved to be statistically significant (P<0.05) indicator. Cattle infected with gastrointestinal nematodes, specifically H. placei, were orally administered with crude aqueous extracts (CAE) and crude methanolic extracts (CME) at gradually higher dosage of 1.0 and 3.0 gm/kg, respectively to evaluate in-vivo anthelmintic efficiency. When administered with 3.0 gm/kg of the body weight, CME showed an ideal decrease of 75.8 and 79.03% parasitic infection but CAE showed 48.88 and 51.11% reduction after 5 and 10 days of treatment, respectively (P<0.05). The overall reduction in eggs per gram was 98.68% in positive controls treated with levamisole HCl. Being an initial investigation of its kind in Pakistan, the outcomes suggested that N. tabacum L. have potential to be used as anti-parasitic agent in ethno-veterinary medication. [ABSTRACT FROM AUTHOR]

Soft corals are marine invertebrates belonging to the class Anthozoa and are rich in bioactive substances that provide their defense and protection from predators, pathogens, and other unfavorable organisms. Seven soft coral species belonging to the genera Sarcophyton and Sinularia were collected from Omani water and extracted and their antibacterial and antifungal properties were tested using the agar-disk diffusion method and a MicroResp technique. Potential compounds that were present in the species were characterized using GC-MS analysis. The results showed that the soft coral species have anti-bacterial activity against Gram-negative bacteria Pseudomonas putida and Pseudomonas tunicata. The GC-MS analysis found the presence of antibacterial, antifungal, antiviral, anticancer, antioxidant agents, agrochemicals, and medicine chemicals. Three novel compounds were found in a Sarcophyton sp. In addition, the compound Andrographolide found in a Sarcophyton sp. has been recently studied as an antiviral agent against SAR-CoV-2. Moreover, the compound Decosane which is found in Sinularia sp. has been used as an anti-parasitic agent against the female Anopheles mosquito to treat malaria in Pakistan. This study highlighted the importance of Omani soft corals as a source of novel bioactive compounds. [ABSTRACT FROM AUTHOR]

A series of 61 thiazolidine-2,4-diones bearing a styryl group at position 5 was synthesized in 2–5 steps and their structure was proved by elemental and spectral analyses. The compounds obtained were evaluated in vitro against the promastigote stage of the kinetoplastid parasite Leishmania infantum and the human HepG2 cell line, to determine selectivity indices and to compare their activities with those of antileishmanial reference drugs. The study of structure–activity relationships indicated the potential of some derivatives bearing a nitro group on the phenyl ring, especially when located at the meta position. Thus, among the tested series, compound 14c appeared as a hit compound with good antileishmanial activity (EC50 = 7 µM) and low cytotoxicity against both the hepatic HepG2 and macrophage THP-1 human cell lines (CC50 = 101 and 121 µM, respectively), leading to good selectivity indices (respectively, 14 and 17), in comparison with the reference antileishmanial drug compound miltefosine (EC50 = 3.3 µM, CC50 = 85 and 30 µM, SI = 26 and 9). Regarding its mechanism of action, among several possibilities, it was demonstrated that compound 14c is a prodrug bioactivated, predominantly by L. donovani nitroreductase 1, likely leading to the formation of cytotoxic metabolites that form covalent adducts in the parasite. Finally, compound 14c is lipophilic (measured CHI LogD7.7 = 2.85) but remains soluble in water (measured PBS solubility at pH7.4 = 16 µM), highlighting the antileishmanial potential of the nitrostyrylthiazolidine-2,4-dione scaffold. [ABSTRACT FROM AUTHOR]

Summary: While there are limited data on the environmental impact of administering equine parasiticide drugs, evidence from other species indicates significant negative ecological effects. Anthelmintic drugs are excreted unchanged or metabolised to other active and/or toxic metabolites that enter the environment through direct excretion. These chemicals can have significant toxic effects on insects, such as dung beetles, earthworms and aquatic animals. Of the frequently used equine anthelmintics, ivermectin is the most ecotoxic; available evidence indicates that moxidectin is less toxic and fenbendazole appears to have little impact on dung‐colonising insects but may be toxic to aquatic organisms and fungi. There are little data regarding the ecotoxicity of pyrantel and praziquantel, although their ecotoxic effects are thought to be low. Pasture hygiene reduces pharmaceutical contamination and also helps to break the endoparasitic cycle of infectivity, thus reducing reliance on anthelmintics. Judicious and targeted use of endoparasiticides, along with pasture hygiene measures, will limit the ecotoxic effects of these drugs as well as reduce the selection pressure that drives anthelmintic resistance. Anthelmintics may also negatively impact the equine gastrointestinal microbiota. Ectoparasiticides (such as fipronil, permethrin and cypermethrin) may also have significant negative ecological effects, with a risk of contamination of both the immediate environment and water courses following topical use of these drugs. The half‐life of fipronil in the environment is variable, but it degrades into compounds which are more toxic; for example, it is highly toxic to bees and is reported to bioaccumulate in fish and can be toxic to birds. Of the synthetic pyrethroids, permethrin degrades at a faster rate than cypermethrin and may therefore have a lower ecotoxic effect. The ecotoxic effects of injectable doramectin are likely to be similar to oral ivermectin, although persistence in faeces may be significantly prolonged compared to the oral treatment route for ivermectin. [ABSTRACT FROM AUTHOR]

The present study investigated the effect of Aceclofenac, a non-steroidal anti-inflammatory drug (NSAID), on the physiology of T. trichopterus (three-spot gourami) as an animal model. Aceclofenac is known for its analgesic and antiinflammatory properties, but its use can lead to severe effects. The study aimed to assess the toxicity of aceclofenac by examining histological changes in the gills and liver, as well as analysing liver marker enzymes in T. trichopterus. The experiment involved a 15-day exposure of disease-free T. trichopterus to a concentration of 0.1 mg aceclofenac/L, while the control group remained untreated. The results demonstrated a significant increase in AspAT and AlaAT activity in fish exposed to aceclofenac compared to the control group. Histopathological examinations revealed necrosis and slight degeneration of gill filaments, as well as hepatocellular degeneration, necrosis, sinusoidal dilatation and cytoplasmic vacuolation in the liver sections of the experimental group. In conclusion, exposure to aceclofenac caused histological alterations in the gills and liver of T. trichopterus, along with elevated AspAT and AlaAT activities, indicating potential liver damage. These findings underscore the potential health risks associated with Aceclofenac use in humans due to Aceclofenac and its metabolites, as well as promoting safe drug use, educating patients about potential risks and implementing regulatory measures that emphasize medical consultation and adherence to prescribed dosages, safeguarding individuals from potential harm, while maximizing the medication's therapeutic benefits. [ABSTRACT FROM AUTHOR]

Compounds originating from animal husbandry can pollute surface water through the application of manure to soil. Typically, grab sampling is employed to detect these residues, which only provides information on the concentration at the time of sampling. To better understand the emission patterns of these compounds, we utilized passive samplers in surface water to collect data at eight locations in a Dutch agricultural region, during different time intervals. As a passive sampler, we chose the integrative-based Speedisk® hydrophilic DVB. In total, we targeted 46 compounds, among which 25 antibiotics, three hormones, nine antiparasitics, and nine disinfectants. From these 46 compounds, 22 compounds accumulated in passive samplers in amounts above the limit of quantification in at least one sampling location. Over the 12-week deployment period, a time integrative uptake pattern was identified in 53% of the examined cases, with the remaining 47% not displaying this behavior. The occurrences without this behavior were primarily associated with specific location, particularly the most upstream location, or specific compounds. Our findings suggest that the proposed use of passive samplers, when compared in this limited context to traditional grab sampling, may provide enhanced efficiency and potentially enable the detection of a wider array of compounds. In fact, a number of compounds originating from animal husbandry activities were quantified for the first time in Dutch surface waters, such as flubendazole, florfenicol, and tilmicosine. The set-up of the sampling campaign also allowed to distinguish between different pollution levels during sampling intervals on the same location. This aspect gains particular significance when considering the utilization of different compounds on various occasions, hence, it has the potential to strengthen ongoing monitoring and mitigation efforts. [ABSTRACT FROM AUTHOR]

Secondary metabolites produced by the fermentation of Streptomyces avermitilis bacterium are powerful antiparasitic agents used in animal health, agriculture and human infection treatments. Avermectin is a macrocyclic lactone with four structural components (A1, A2, B1, B2), each of them containing a major and a minor subcomponent, out of which avermectin B1a is the most effective parasitic control compound. Avermectin B1a produces two homologue avermectins (B1 and B2) that have been used in agriculture as pesticides and antiparasitic agents, since 1985. It has a great affinity with the Cl-channels of the glutamate receptor, allowing the constant flow of Cl- ions into the nerve cells, causing a phenomenon of hyperpolarization causing death by flaccid paralysis. The purpose of this work was to gather information on the production of avermectins and their biocidal effects, with special emphasis on their role in the control of pests and phytopathogenic diseases. The literature showed that S. avermitilis is an important producer of macrocyclic lactones with biocidal properties. In addition, avermectin contributes to the control of ectoparasites and endoparasites in human health care, veterinary medicine and agriculture. Importantly, avermectin is a compound that is harmless to the host (no side effects), non-target organisms and the environment. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the anti-leishmanial effects of curcumin nanoemulsion (CUR-NE) against Leishmania major (MRHO/IR/75/ER) in both in vitro and in vivo experiments. CUR-NE was successfully prepared via the spontaneous emulsification method. The in vitro effect of various concentrations of CUR-NE against L. major promastigotes was assessed using the flow cytometry method. In vivo experiments were carried out in BALB/c mice inoculated subcutaneously with 2 × 106 L. major promastigotes. Mice were treated with topical CUR-NE (2.5 mg/ml), intra-lesion injection of CUR-NE (2.5 mg/ml), topical CUR suspension (CUR-S, 2.5 mg/ml), topical NE without CUR (NE-no CUR), amphotericin B as the positive control group, and infected untreated mice as the negative control group. In vitro exposure of promastigotes to CUR-NE showed a dose-dependent anti-leishmanial effect, with a 67.52 ± 0.35% mortality rate at a concentration of 1250 µg/ml and an IC50 of 643.56 µg/ml. In vivo experiments showed that topical CUR-NE and CUR-S significantly decreased the mean lesion size in mice after four weeks from 4.73 ± 1.28 to 2.78 ± 1.28 mm and 4.45 ± 0.88 to 3.23 ± 0.59 mm, respectively (p = 0.001). Furthermore, CUR-NE significantly decreased the parasite load in treated mice compared with the negative control group (p = 0.001). Results from the current study demonstrated the promising activity of CUR-NE against L. major in both in vitro and in vivo experiments. Moreover, CUR-NE was more efficient than CUR-S in healing and reducing parasite burden in mouse models. Future studies should aim to identify molecular mechanisms as well as the pharmacologic and pharmacokinetic aspects of CUR-NE. [ABSTRACT FROM AUTHOR]

Anesthetics such as benzocaine, eugenol, and menthol are commonly used in fish in sustainable aquaculture practices. There is growing interest in exploring their beneficial antiparasitic properties. Cheirodon interruptus is a small native freshwater baitfish widely used in Argentina, South America. There is limited literature on the effects of different anesthetic and antiparasitic agents in C. interruptus. Thus, the aim of the present study was to evaluate the anesthetic and antiparasitic effects of benzocaine, eugenol and menthol in C. interruptus. A total of 165 C. interruptus adults were collected from a natural stream of the Salado River basin, Buenos Aires, Argentina. Fish were divided in 15 groups (n = 10) and exposed to different treatments: eugenol 10, 20, 50, 80 and100 mgL−1; benzocaine 20, 50, 80, 110 and140 mgL−1 and menthol 25, 50, 75, 100 and 125 mg L−1. Based on the idea that a good anesthetic induces sedation in less than 180 s and allows recovery in less than 300 s, results indicated that 20 mg L−1 eugenol, 125 mg L−1 menthol and 80 mg L−1 benzocaine meet the requirements for use as good anesthetics in C. interruptus. In addition, their antiparasitic effects were evaluated by assessing differences in the mean abundance of the monogenean Diaphorocleidus sp. Most of concentrations tested showed differences in the mean abundance of Diaphorocleidus sp. Eugenol 20 mg L−1 and benzocaine 80 mg L−1 decreased the parasite mean abundance, whereas menthol 125 mg L−1 showed no significant differences with the controls. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Repurposed medications for acute coronavirus disease 2019 (COVID-19) continued to be prescribed after results from rigorous studies and national guidelines discouraged use. We aimed to describe prescribing rates of nonrecommended medications for acute COVID-19 in children, associations with demographic factors, and provider type and specialty. METHODS: In this retrospective cohort of children <18 years in a large United States all-payer claims database, we identified prescriptions within 2 weeks of an acute COVID-19 diagnosis.We calculated prescription rate, performed multivariable logistic regression to identify risk factors, and described prescriber type and specialty during nonrecommended periods defined by national guidelines. RESULTS: We identified 3082626 COVID-19 diagnoses in 2 949 118 children between March 7, 2020 and December 31, 2022. Hydroxychloroquine (HCQ) and ivermectin were prescribed in 0.03% and 0.14% of COVID-19 cases, respectively, during nonrecommended periods (after September 12, 2020 for HCQ and February 5, 2021 for ivermectin) with considerable variation by state. Prescription rates were 4 times the national average in Arkansas (HCQ) and Oklahoma (ivermectin). Older age, nonpublic insurance, and emergency department or urgent care visit were associated with increased risk of either prescription. Additionally, residence in nonurban and low-income areas was associated with ivermectin prescription. General practitioners had the highest rates of prescribing. CONCLUSIONS: Although nonrecommended medication prescription rates were low, the overall COVID-19 burden translated into high numbers of ineffective and potentially harmful prescriptions. Understanding overuse patterns can help mitigate downstream consequences of misinformation. Reaching providers and parents with clear evidence-based recommendations is crucial to children's health. [ABSTRACT FROM AUTHOR]

The article determines the in vivo insecticidal activity of the antiparasitic drug "Superium Panacea" for cats. It has been established that the drug "Superium Panacea" has a pronounced insecticidal effect on wingless ectoparasitic insects Ctenocephalides felis and acaricidal effect on sarcoptoid ticks Otodectes cynotis. The duration of the protective effect of the drug was at least 28 days. The drug "Superium Panacea" with a wide spectrum of insecticidal and acaricidal action when applied to cats and kittens orally (peros), individually, once, during morning feeding with a small amount of feed or forcibly, according to the manufacturer's recommended schemes, is well tolerated by animals of different breeds and ages, which were used in the study and can be used for the treatment and prevention of mixed parasitosis. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis is a zoonotic parasitic disease that affects the liver in more than 70% of cases, and there is still an underestimated incidence in endemic areas. With a peculiar clinical presentation that ranges from paucisymptomatic illness to severe and possibly fatal complications, quality imaging and serological studies are required for diagnosis. The mainstay of treatment to date is surgery combined with antiparasitic agents. The surgical armamentarium consists of open and laparoscopic procedures for selected cases with growing confidence in parenchyma-sparing interventions. Endoscopic retrograde cholangiopancreatography (ERCP) is extremely useful for the diagnosis and treatment of biliary fistulas. Recent relevant studies in the literature are reviewed, and two complex cases are presented. The first patient underwent open surgery to treat 11 liver cysts, and during the follow-up, a right pulmonary cyst was diagnosed that was treated by minimally invasive surgery. The second case is represented by the peritoneal rupture of a giant liver cyst in a young woman who underwent laparoscopic surgery. Both patients developed biliary fistulas that were managed by ERCP. Both patients exhibited a non-specific clinical presentation and underwent several surgical procedures combined with antiparasitic agents, highlighting the necessity of customized treatment in order to decrease complications and successfully cure the disease. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 μM against M. abscessus type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against M. abscessus were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of M. abscessus from 0.625 μM to 2.5 μM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time–kill curve study and also electron microscopy study. Interestingly, it was found that at 128 μg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 μg/mL, 99% at 32 μg/mL, and 90% at 16 μg/mL. Therefore, bithionol may be a potential candidate for the treatment of M. abscessus infections due to its significant antimicrobial and antibiofilm activities. [ABSTRACT FROM AUTHOR]

Simple Summary: To treat canine leishmaniosis, two medication combinations are used: meglumine antimoniate with allopurinol, or miltefosine with allopurinol. This study compared the clinical effectiveness of both options after one month of treatment. The results showed a significantly higher rate of complete clinical cure in the meglumine antimoniate and allopurinol group. Most dogs in both groups improved after one month of treatment. There were no significant differences in the presence of the Leishmania parasite between the groups after treatment. The humoral immune response could not be compared due to insufficient data. Overall, meglumine antimoniate and allopurinol seem more effective in treating canine leishmaniosis compared to miltefosine and allopurinol. The treatment of canine leishmaniosis commonly involves meglumine antimoniate with allopurinol or miltefosine with allopurinol. This study aims to compare the clinical and clinicopathological efficacy at 28–30 days of conventional dosing regimens for both treatments using the critically appraised topic methodology. A comprehensive search across three databases (PubMed, CAB Abstracts, and Web of Science) from March 2004 to September 2023 yielded 16 relevant articles, encompassing 325 ogs treated with meglumine antimoniate and allopurinol, and 273 dogs treated with miltefosine and allopurinol. The findings indicated a significantly higher rate of complete clinical cure in the group treated with meglumine antimoniate and allopurinol. Most dogs in both groups exhibited improvement in clinicopathological alterations after one month of treatment. No significant difference was observed in the number of dogs that showed a negative Leishmania qPCR between the two groups, one month post-treatment. However, quantitative serology results were not commonly reported in the available data and therefore this aspect could not be compared. [ABSTRACT FROM AUTHOR]

Purpose: Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone–coumarin hybrids QC1–QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. Methods: The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. Results: The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques (P < 0.05). Conclusion: Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents. [ABSTRACT FROM AUTHOR]

Nitrogenous heterocyclic rings are present in a wide range of drugs, natural compounds, and fine chemicals and are considered privileged scaffolds in medicinal chemistry. Seeking novel anti‐protozoal drugs acting on new targets or by novel mechanisms of action, we focused on a preliminary evaluation of the potential of "linear‐shaped" diaryl pyrazines. To this purpose, a two‐enzyme chemoenzymatic synthesis of this heteroaromatic core was carried out. Specifically, starting from simple, commercially available aromatic aldehydes, the target pyrazines were obtained through a sequence of biocatalytic benzoin condensation, chemical oxidation and a transaminase‐mediated tandem process of transamination and cyclization. The profiles of the compounds as antiprotozoal agents were evaluated in vitro against parasites cultures of the Leishmania and Plasmodium genera and using the human cell line HepG2. [ABSTRACT FROM AUTHOR]

The Stachys L. genus has been widely used in traditional medicine in many countries throughout the world. The study aimed to investigate the chemical composition and bioactivity of the hydroethanolic extract (50% v/v) obtained by ultrasonication from the aerial flowering parts of Stachys sylvatica L. (SSE) collected in Almaty region (Southern Kazakhstan). According to RP-HPLC/PDA analysis the leading metabolites of the SSE belonged to polyphenols: chlorogenic acid and its isomers (2.34 mg/g dry extract) and luteolin derivatives (1.49 mg/g dry extract), while HPLC-ESI-QTOF-MS/MS-based qualitative fingerprinting revealed the presence of 17 metabolites, mainly chlorogenic acid and its isomers, flavonoid glycosides, and verbascoside with its derivatives. GC-MS analysis of the volatile metabolites showed mainly the presence of diterpenoids and fatty acid esters. A reduction in the viability of nematodes Rhabditis sp. was obtained for the SSE concentration of 3.3 mg/mL, while 11.1 mg/mL showed activity comparable to albendazole. The SSE exhibited higher activity against Gram-positive (MIC = 0.5-2 mg/mL) than Gram-negative bacteria and yeast (MIC = 8 mg/mL), exerting bactericidal and fungicidal effects but with no sporicidal activity. The SSE showed some antiviral activity against HCoV-229E replicating in MRC-5 and good protection against the cytopathic effect induced by HHV-1 in VERO. The SSE was moderately cytotoxic towards human cervical adenocarcinoma (H1HeLa) cells (CC50 of 0.127 mg/mL after 72 h). This study provides novel information on the SSE extract composition and its biological activity, especially in the context of the SSE as a promising candidate for further antiparasitic studies. [ABSTRACT FROM AUTHOR]

Solanum is the largest genus within the Solanaceae family and has garnered considerable attention in chemical and biological investigations over the past 30 years. In this context, lobeira or "fruta-do-lobo" (Solanum lycocarpum St. Hill), a species predominantly found in the Brazilian Cerrado, stands out. Beyond the interesting nutritional composition of the fruits, various parts of the lobeira plant have been used in folk medicine as hypoglycemic, sedative, diuretic, antiepileptic, and antispasmodic agents. These health-beneficial effects have been correlated with various bioactive compounds found in the plant, particularly alkaloids. In this review, we summarize the alkaloid composition of the lobeira plant and its biological activities that have been reported in the scientific literature in the last decades. The compiled data showed that lobeira plants and fruits contain a wide range of alkaloids, with steroidal glycoalkaloid solamargine and solasonine being the major ones. These alkaloids, but not limited to them, contribute to different biological activities verified in alkaloid-rich extracts/fractions from the lobeira, including antioxidant, anti-inflammatory, anticancer, antigenotoxic, antidiabetic, antinociceptive, and antiparasitic effects. Despite the encouraging results, additional research, especially toxicological, pre-clinical, and clinical trials, is essential to validate these human health benefits and ensure consumers' safety and well-being. [ABSTRACT FROM AUTHOR]

Sophocarpine is a natural compound that belongs to the quinolizidine alkaloid family, and has a long history of use and widespread distribution in traditional Chinese herbal medicines such as Sophora alopecuroides L., Sophora flavescens Ait., and Sophora subprostrata. This article aims to summarize the pharmacology, pharmacokinetics, and toxicity of sophocarpine, evaluate its potential pharmacological effects in various diseases, and propose the necessity for further research and evaluation to promote its clinical application. A large number of studies have shown that it has anti-inflammatory, analgesic, antiviral, antiparasitic, anticancer, endocrine regulatory, and organ-protective effects as it modulates various signaling pathways, such as the NF-κB, MAPK, PI3K/AKT, and AMPK pathways. The distribution of sophocarpine in the body conforms to a two-compartment model, and sophocarpine can be detected in various tissues with a relatively short half-life. Although the pharmacological effects of sophocarpine have been confirmed, toxicity and safety assessments and reports on molecular mechanisms of its pharmacological actions have been limited. Given its significant pharmacological effects and potential clinical value, further research and evaluation are needed to promote the clinical application of sophocarpine. [ABSTRACT FROM AUTHOR]