Antiparasitic Research Articles

Structure and activity of amphiphilic PEO-PPO-based polymeric micelles and gels incorporating host–guest complexes of miltefosine as novel formulations for the treatment of leishmaniasis

Hypothesis: Poloxamines are amphiphilic block copolymers that self-assemble forming polymeric micelles (PMs) and hydrogels. They have emerged as promising colloidal carriers for their potential in improving drug delivery and controlled release through their multi-responsive properties. Tetronic® 1307 (T1307) PMs and gels have been used herein as vehicles of host–guest complexes of cyclodextrins (CDs) and miltefosine (MF), an amphiphilic, anti-parasitic drug effective against leishmaniasis.Experiments: The association of MF to αCD, βCD, and HPβCD and the topology of the complexes have been fully characterized by NMR spectroscopy. Then, the structure of the complex-loaded PMs and hydrogels investigated using diffusion nuclear magnetic resonance (DOSY), small angle neutron scattering (SANS), and dynamic light scattering (DLS). The antileishmanial activity of the constructs was evaluated against Leishmania major promastigotes and amastigotes, as well as their cytotoxicity in macrophages.Findings: All the CDs investigated form highly stable inclusion complexes with MF in a 2CD:1MF stoichiometry that lead to considerable proportions of complexed drug at high dilution, the HPβCD providing the highest stability and compatibility with the poloxamine. The complex incorporates preferentially into the hydrophilic shell of the PMs, inducing the elongation of the aggregates and the dehydration of the micellar core, formed mainly by the PPO blocks. At high concentration of polymer and physiological temperature, the complex-loaded PMs pack in a BCC-type paracrystal network. The micellar formulations of the CD-complexed MF reduced the cytotoxicity of the drug, while enhancing its antileishmanial activity. This approach could improve the currently available treatments, facilitating the administration of MF at lower concentrations and achieving relevant therapeutic effects, not only through the intravenous route, but also as topical formulations through injectable thermogels for the treatment of the cutaneous and mucocutaneous forms of the disease.

Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts

Heart failure (HF) is manifested by transcriptional and post-transcriptional reprogramming of critical genes. Multiple studies have revealed that microRNAs could translocate into subcellular organelles such as nucleus to modify gene expression. However, the functional property of subcellular Argonaute2 (AGO2), the core member of the microRNA machinery, has remained elusive in HF. AGO2 was found to be localized in both cytoplasm and nucleus of cardiomyocytes, and robustly increased in failing hearts of patients and animal models. We demonstrated nuclear AGO2 rather than cytosolic AGO2 overexpression by recombinant adeno-associated virus (serotype 9) with cardiomyocyte-specific troponin T promoter exacerbated the cardiac dysfunction in transverse aortic constriction (TAC)-operated mice. Mechanistically, nuclear AGO2 activates the transcription of ANKRD1, encoding Ankyrin repeat domain-containing protein 1 (ANKRD1), which also has a dual function in the cytoplasm as part of I-band of the sarcomere and in the nucleus as a transcriptional cofactor. Overexpression of nuclear ANKRD1 recaptured some key features of cardiac remodeling by inducing pathological MYH7 activation, whereas cytosolic ANKRD1 seemed cardio-protective. For clinical practice, we found ivermectin, an anti-parasite drug, and ANPep, a ANKRD1 nuclear location signal mimetic peptide, were able to prevent ANKRD1 nuclear import, resulting in the improvement of cardiac performance in TAC-induced HF.

Induction of IFIT1/IFIT3 and inhibition of Bcl-2 orchestrate the treatment of myeloma and leukemia via pyroptosis

Induction of pyroptosis is proposed as a promising strategy for the treatment of hematological malignancies, but little is known. In the present study, we find clioquinol (CLQ), an anti-parasitic drug, induces striking myeloma and leukemia cell pyroptosis on a drug screen. RNA sequencing reveals that the interferon-inducible genes IFIT1 and IFIT3 are markedly upregulated and are essential for CLQ-induced GSDME activation and cell pyroptosis. Specifically, IFIT1 and IFIT3 form a complex with BAX and N-GSDME therefore directing N-GSDME translocalization to mitochondria and increasing mitochondrial membrane permeabilization and triggering pyroptosis. Furthermore, venetoclax, an activator of BAX and an inhibitor of Bcl-2, displays strikingly synergistic effects with CLQ against leukemia and myeloma via pyroptosis. This study thus reveals a novel mechanism for mitochondrial GSDME in pyroptosis and it also illustrates that induction of IFIT1/T3 and inhibition of Bcl-2 orchestrate the treatment of leukemia and myeloma via pyroptosis.

Assessing the utilization patterns of antiparasitic drug and farmer’s perception: implications for resistance in India's dairy farming sector

Assessing the utilization patterns of antiparasitic drug and farmer’s perception: implications for resistance in India's dairy farming sector

Green Synthesis of Uncoated and Olive Leaf Extract-Coated Silver Nanoparticles: Sunlight Photocatalytic, Antiparasitic, and Antifungal Activities.

The circular economy, which attempts to decrease agricultural waste while also improving sustainable development through the production of sustainable products from waste and by-products, is currently one of the main objectives of environmental research. Taking this view, this study used a green approach to synthesize two forms of silver nanoparticles: coated silver nanoparticles with olive leaf extract (Ag-olive) and uncoated pure silver nanoparticles (Ag-pure), which were produced by the calcination of Ag-olive at 550 °C. The extract and the fabricated nanoparticles were characterized by a variety of physicochemical techniques, including high-performance liquid chromatography (HPLC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Adult ticks (Hyalomma dromedarii) (Acari: Ixodidae) were used in this study to evaluate the antiparasitic activity of synthesized nanoparticles and extract. Furthermore, the antifungal activity was evaluated against Aspergillus aculeatus strain N (MW958085), Fuserium oxysporum (MT550034), and Alternaria tenuissiuma (MT550036). In both antiparasitic and antifungal tests, the as-synthesized Ag-olive showed higher inhibition activity than Ag-pure and olive leaf extract. The findings of this research suggest that Ag-olive may be a powerful and eco-friendly antiparasitic and antifungal agent. Ag-pure was also evaluated as a photocatalyst under sunlight for the detoxification of Eri-chrome-black T (EBT), methylene blue (MB), methyl orange (MO), and rhodamine B (RhB).

Bilharzial Appendicitis: About A Case, at the District Hospital of Commune IV of Bamako

Bilharzial appendicitis is a very rare condition. We report the case of a young 18-year-old adolescent admitted to the department for pain in the right iliac fossa in a febrile context, evolving for 8 days with a history of terminal hematuria. After an abdominal ultrasound, the diagnosis of acute appendicitis was made. Treatment consisted of an appendectomy. The pathological examination revealed eggs of Schistosoma hematobium at the level of the appendicular wall. An antiparasitic treatment based on praziquantel was started. The postoperative course was simple.

Anti-Trichomonas vaginalis Activity of Marine Ascidians (Tunicates; Ascidiacea) from the Bushehr Province, Iran.

The aim of the current research is to evaluate the antiparasite effects of compounds isolated from marine ascidian tunicates on Trichomonas vaginalis. Ascidian tunicates after collection were cut into small pieces, freeze-dried, and powdered. The resulting material was subjected to extraction in double-distilled water, ethanol, n-hexane, and dichloromethane. To fractionate the extracts and identify the most bioactive compound, silica gel column chromatography and GC-M/S analysis were used. Fraction 18 of silica gel column chromatography of ethanol extract was the most effective against T. vaginalis. The respective IC50, CC50, and SI values for fraction 18 were 28.62 μg/mL, ˃800 μg/mL, and ˃27.95. GC-M/S analysis of this fraction identified a major phenolic compound (2, 4-bis (1, 1-dimethyl ethyl), whose toxicity against vero cells was only 10.15%. The ethanolic fraction containing phenol-2,4-bis (1,1-dimethylethyl), which has a potent lethality effect on T. vaginalis, may be considered as an antiparasite drug candidate.

PHARMACOKINETICS AND EFFICACY OF A SINGLE TOPICAL DOSE OF EPRINOMECTIN IN GIRAFFE (GIRAFFA SPP.).

Growing resistance to current antiparasitic medications, both in livestock and in zoological species under human care, makes it imperative to evaluate available drugs on the market, such as eprinomectin. In this prospective study, five males and one female of reticulated (Giraffa reticulata; n = 2), Masai (Giraffa tippelskirchii; n = 1), Nubian (Giraffa camelopardalis; n = 2), and hybrid subspecies (n = 1) of giraffe, received 1.5 mg/kg eprinomectin topically along the dorsum. Using high-performance liquid chromatography, concentrations of eprinomectin in plasma samples collected at 0, 4, 24, and 48 h, and 7, 14, 21, and 28 d were evaluated following drug administration. Complete blood cell counts and biochemistry panels were performed before (n = 6) and after (n = 3) eprinomectin administration. Samples for modified double centrifugal fecal flotation (n = 6) were evaluated prior to eprinomectin administration to evaluate for endoparasites and were repeated after the study (n = 5). Noncompartmental pharmacokinetic analysis was applied to the data. The observed maximum plasma concentration was 11.45 ng/ml and the time of observed maximum concentration was 2.67 d. The mean terminal half-life was 5.16 d. No adverse effects were observed related to eprinomectin administration and no blood work changes were observed. Parasite loads decreased (n = 3) or did not change (n = 2) after eprinomectin administration. The mean peak plasma concentration of eprinomectin in giraffe was similar to that achieved in cattle, despite using three times the dose.

A case of co-infection with head lice and varicella in a child: considerations for rational management

A case of co-infection with head lice and varicella in a child: considerations for rational management

A comparative study on the chemical composition, anti-microbial, antiparasitic, and cytotoxic activities of Rhanterium adpressum Coss. & Dur. and Rhanterium suaveolens Desf. essential oils from Algeria

The aim of the present study was to evaluate and compare the chemical composition, antimicrobial, antiparasitic, and cytotoxic properties of the essential oils extracted from Rhanterium adpressum Coss. & Dur. (EORA) and Rhanterium suaveolens Desf. (EORS). The main compounds of EORA were myrcene (18.51%), α-pinene (14.36%), sabinene (13.55%), β-pinene (5.67%), and camphene (5.39%). While camphene (25.06%), α-pinene (13.14%), myrcene (9.74%), sabinene (8.27%), D-limonene (7.86%), and β-pinene (7.34%) constituted the major components of EORS. A potent antibacterial activity was also recorded against Escherichia coli with MIC = 5.72 mg/mL for EORA and MIC = 5.96 mg/mL for EORS. Concerning the antifungal effect, a remarkable efficiency was exerted against the two tested Candida albicans strains (MIC < 5.96 mg/mL) for EORS and against Candida albicans 26 (MIC = 5.72 mg/mL) for EORA. Furthermore, a promising antiparasitic ability was observed against Acanthamoeba castellanii (IC50 = 6.42±0.21 μg/mL) for EORS and against Leishmania amazonensis (IC50=9.66±1.46 μg/mL) for EORA. However, low cytotoxicity was recorded against macrophages J774-A1 (LC50 = 67.68±4.02 μg/mL) only for EORS. Based on the present findings, it may be concluded that the two tested EOs possess significant antimicrobial and antiparasitic activities with minimal cytotoxicity, so they can be used as new sources of antimicrobial and antiparasitic drugs.

A data compilation of antibiotic treatments in Canadian finfish aquaculture from 2016 to 2021 and the cumulative usage of antibiotics and antiparasitic drugs at marine sites

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 &lt;30% of sites used two drugs per year and &lt;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.

Light microscopical and parasitological analyses revealed the beneficial effects of silver nanoparticles and various myrrh extracts against Trichinella spiralis infection in mice.

Trichinella spiralis infection is a food-borne zoonotic disease caused by nematodes that dwell in the tissues, presenting a significant public health concern. This study aimed to evaluate the effectiveness of different treatments including silver nanoparticles (AgNPs), myrrh biosynthesized AgNPs "AgNPs synthesized using plant-based green technologies", myrrh extract, and myrrh essential oil, as alternative treatments against T. spiralis infection. Parasitological, histopathological, and cytotoxicity assessments were conducted to investigate the effects of various concentrations of these treatments in reducing the populations of adult worms and larvae during both the intestinal and muscular phases of T. spiralis-infected mice. The results showed that the highest antihelminthic efficacy against the intestinal phase of T. spiralis was achieved by myrrh extract (86.66%), followed closely by AgNPs (84.96%) and myrrh AgNPs (82.51%) at higher concentrations (800 mg/kg for myrrh extract, 40 μg/mL for AgNPs, and 40 μg/mL for myrrh AgNPs). While the group treated with myrrh essential oil showed the lowest percentage of adult reduction (78.14%). However, all treatments demonstrated comparable effects in reducing the larvae population in the muscle phase. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. Additionally, a comprehensive assessment of the cytotoxicity of AgNPs indicated low toxicity levels. This study supports that AgNPs synthesized using plant-based green technologies hold therapeutic potential for the treatment of T. spiralis infection. These findings present a promising avenue for the development of novel antiparasitic drugs that are both effective and safe. RESEARCH HIGHLIGHTS: Myrrh extract has the highest antihelminthic efficacy against the intestinal phase of T. spiralis. Histopathological examination of the tissues revealed compelling evidence of the effectiveness of AgNPs, particularly when prepared with myrrh. During intestinal phase of T. spiralis, varying levels of nanoparticle precipitation were detected in the liver, brain, lung, and intestine. During the muscular phase, the highest amount of AgNPs precipitation was detected in the liver, followed by the brain, and lung.

Exploring the Efficacy of Pellitorine as an Antiparasitic Agent Against Argulus: Impacts on Antioxidant Levels and Immune Responses in Goldfish (Carassius auratus).

Argulus spp. infestation is a significant challenge for aquaculture, currently, there are no approved medications available to efficiently manage this parasite. Consequently, mechanical removal of parasites using forceps and natural substances like herbs are being explored as alternative treatment methods. Pellitorine (PLE) is a naturally occurring compound found in several plant species. It is classified as an alkaloid and belongs to the class of compounds known as amides. This study aimed to evaluate the effectiveness of PLE in preventing Argulus spp. infestations in goldfish (Carassius auratus) and to determine the optimal dosage of PLE for the detachment of Argulus spp. The findings of this study revealed that PLE enhanced the immune response of goldfish by promoting superoxide dismutase (SOD) and catalase (CAT) in Argulus-infected goldfish. Additionally, PLE induces reactive oxygen species (ROS) generation and cellular damage in the Argulus. PLE at a dosage of 5mg/mL was able to detach 80% of the argulus from goldfish within 12h. Therapeutic index was found to be 5.99, suggesting that PLE is the safest drug. Therefore, our findings suggest that PLE can be a suitable and effective treatment option for preventing Argulus infestations in goldfish. The results of this study can guide the use of PLE at an optimal dosage to control Argulus infestation in goldfish.

Evaluation of anthelminthic and antiprotozoal activity of myrrh (Commiphora myrrha) methanolic extract.

To treat and control parasitic infections, traditional medical remedies using plant products are utilized as antiparasitic agents rather than standard synthetic chemicals due to drug resistance. Myrrh, a resinous exudate of Commiphora myrrha (Burseraceae), is a powerful antioxidant with a variety of medicinal uses. This study aimed to investigate the effect of the myrrh methanolic extract (MyE) of three concentrations (100, 50, and 25 mg/ml) on the sporulation of oocysts and as an anthelminthic effector via in vitro study. Characterization of the plant was done by Fourier-transform infrared spectroscopy (FT-IR). The earthworm, Eisenia fetida, is used as a model worm to evaluate the anthelminthic activity of MyE. Eimeria labbeana-like oocysts are used as a model protozoan parasite in anticoccidial assays. The sporulation and inhibition (%) of E. labbeana-like were assessed by MyE compared to other chemical substances. FT-IR revealed the presence of twelve active compounds. Our results showed that paralysis and death of earthworms at MyE (100 mg/ml) were 7.88 ± 0.37 and 9.24 ± 0.60 min, respectively, which is more potency when compared to mebendazole (reference drug). In all treated worms, microscopic examinations revealed obvious surface architecture abnormality. This study shows that MyE affects oocysts sporulation in a dose-dependent manner. At 24 and 36 hr, a high concentration of MyE (100 mg/ml) inhibits sporulation by 90.95 and 87.17 %. At 36 hr, other concentrations of MyE (50 and 25 mg/ml), as well as amprolium, DettolTM, and phenol inhibits oocyst sporulation by 40.17 %, 29.34 %, 45.09 %, 85.11 %, and 61.58 %, respectively. According to our research, the MyE extract had powerful anthelmintic and anticoccidial properties.

Ivermectin Inhibits Bladder Cancer Cell Growth and Induces Oxidative Stress and DNA Damage.

Bladder cancer is the most common malignant tumor of the urinary system. Nevertheless, current therapies do not provide satisfactory results. It is imperative that novel strategies should be developed for treating bladder cancer. To evaluate the effect of a broad-spectrum anti-parasitic agent, Ivermectin, on bladder cancer cells in vitro and in vivo. CCK-8 and EdU incorporation assays were used to evaluate cell proliferation. Apoptosis was detected by flow cytometry, TUNEL assay, and western blotting. Flow cytometry and DCFH-DA assay were used to analyze the reactive oxygen species (ROS) levels. DNA damage was determined by Neutral COMET assay and γ H2AX expression. Proteins related to apoptosis and DNA damage pathways were determined by WB assay. Xenograft tumor models in nude mice were used to investigate the anti-cancer effect of Ivermectin in vivo. Our study showed that in vitro and in vivo, Ivermectin inhibited the growth of bladder cancer cells. In addition, Ivermectin could induce apoptosis, ROS production, DNA damage, and activate ATM/P53 pathwayrelated proteins in bladder cancer cells. According to these findings, Ivermectin may be a potential therapeutic candidate against bladder cancer due to its significant anti-cancer effect.

Whole genome case-control study of central nervous system toxicity due to antimicrobial drugs.

A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2.

Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues.

Despite tremendous advances in the prevention and treatment of infectious diseases, only few antiparasitic drugs have been developed to date. Protozoan infections such as malaria, leishmaniasis, and trypanosomiasis continue to exact an enormous toll on public health worldwide, underscoring the need to discover novel antiprotozoan drugs. Recently, there has been an explosion of research into the antiprotozoan properties of quercetin, one of the most abundant flavonoids in the human diet. In this review, we tried to consolidate the current knowledge on the antiprotozoal effects of quercetin and to provide the most fruitful avenues for future research. Quercetin exerts potent antiprotozoan activity against a broad spectrum of pathogens such as Leishmania spp., Trypanosoma spp., Plasmodium spp., Cryptosporidium spp., Trichomonas spp., and Toxoplasma gondii. In addition to its immunomodulatory roles, quercetin disrupts mitochondrial function, induces apoptotic/necrotic cell death, impairs iron uptake, inhibits multiple enzymes involved in fatty acid synthesis and the glycolytic pathways, suppresses the activity of DNA topoisomerases, and downregulates the expression of various heat shock proteins in these pathogens. In vivo studies also show that quercetin is effective in reducing parasitic loads, histopathological damage, and mortality in animals. Future research should focus on designing effective drug delivery systems to increase the oral bioavailability of quercetin. Incorporating quercetin into various nanocarrier systems would be a promising approach to manage localized cutaneous infections. Nevertheless, clinical trials are needed to validate the efficacy of quercetin in treating various protozoan infections.

Route of exposure to veterinary products in bees: Unraveling pasture's impact on avermectin exposure and tolerance in stingless bees.

Deforestation rapidly increases in tropical regions, primarily driven by converting natural habitats into pastures for extensive cattle ranching. This landscape transformation, coupled with pesticide use, are key drivers of bee population decline. Here, we investigate the impact of pasture-dominated landscapes on colony performance, pesticide exposure, and insecticide sensitivity of the stingless bee Tetragonisca angustula. We monitored 16 colonies located in landscapes with varying proportions of pasture. We collected bee bread for pesticide and palynological analysis. We found a positive correlation between pollen diversity and colony growth, with no effect of the proportion of pasture in the landscape. In contrast, we detected prevalent and hazardous concentrations of the insecticide abamectin (9.6-1,856 µg/kg) in bee bread, which significantly increased with a higher proportion of pasture. Despite the abamectin exposure, the bee colonies displayed no adverse effects on their growth, indicating a potential tolerance response. Further investigations revealed that bees from sites with higher proportions of pasture showed significantly reduced mortality when exposed to a lethal concentration of abamectin (0.021 µg/µL) after 48 h. Since abamectin is scarcely used in the study area, we designed an experiment to track ivermectin, a closely related antiparasitic drug used in cattle. Our findings uncovered a new exposure route of bees to pesticides, wherein ivermectin excreted by cattle is absorbed and biotransformed into abamectin within flowering plants in the pastures. These results highlight that unexplained exposure routes of bees to pesticides remain to be described while also revealing that bees adapt to changing landscapes.

Antiparasitic activity of the iron-containing milk protein lactoferrin and its potential derivatives against human intestinal and blood parasites

An iron-containing milk protein named lactoferrin (Lf) has demonstrated antiparasitic and immunomodulatory properties against a variety of human parasites. This protein has shown its capability to bind and transport iron molecules in the vicinity of the host–pathogen environment. The ability of parasites to sequester the iron molecule and to increase their pathogenicity and survival depends on the availability of iron sources. Lf protein has suggested a iron chelating effect on parasites iron and, hence, has shown its antiparasitic effect. Since the parasites have a complex life cycle and have developed drug resistance, vaccines and other treatments are a handful. Therefore, therapeutic research focusing on natural treatment regimens that target the parasite and are non-toxic to host cells is urgently needed. The antiparasitic efficacy of Lf protein has been extensively studied over the past 40 years using both in vitro and in vivo studies. This review article highlighted past important studies on Lf protein that revealed its potential antiparasitic activity against various intracellular and extracellular intestinal or blood-borne human parasites. This review article structures the role of Lf protein in its various forms, such as native, peptide, and nanoformulation, laying the groundwork for its function as an antiparasitic agent and its possible known mechanisms of action.

Chemical Structure Elucidation in the Development of Inorganic Drugs: Evidence from Ru‐, Au‐, As‐, and Sb‐based Medicines

AbstractStructure elucidation plays a critical role across the landscape of medicinal chemistry, including medicinal inorganic chemistry. Herein, we discuss the importance of structure elucidation in drug development and then provide three vignettes that capture key instances of its relevance in the development of biologically active inorganic compounds. In the first, we describe the exploration of the biological activity of the trinuclear Ru compound called ruthenium red and the realization that this activity derived from a dinuclear impurity. We next explore the development of Au‐based antitubercular and antiarthritic drugs, which features a key step whereby ligands were discovered to bind to Au through S atoms. The third exposition traces the development of As‐based antiparasitic drugs, a key step of which was the realization that the reaction of arsenic acid and aniline does not produce an anilide of arsenic acid, as originally thought, but rather an amino arsonic acid. These case studies provide the motivation for an outlook in which the development of Sb‐based antiparasitic drugs is described. Although antileishmanial pentavalent antimonial drugs remain in widespread use to this day, their chemical structures remain unknown.