Search Results (422)

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Arginine kinase is a key phosphagen kinase in invertebrates that facilitates rapid ATP regeneration by reversibly transferring phosphate groups between phosphoarginine and ADP. Structural studies have shown that the enzyme adopts distinct conformations in its ligand-free and ligand-bound states, known as the “open” and “closed” forms, respectively. These conformational changes are crucial for catalytic activity, enabling precise positioning of active-site residues and loop closure during phosphoryl transfer. Transition-state analog complexes have provided additional insights by mimicking intermediate states of catalysis, supporting the functional relevance of the open/closed structural model. Furthermore, studies across multiple species reveal how monomeric and dimeric forms of arginine kinase contribute to its allosteric regulation and substrate specificity. Beyond its metabolic role, arginine kinase is also recognized as a major allergen in crustaceans. Its structural uniqueness and absence in vertebrates make it a promising candidate for selective drug targeting. By integrating crystallographic data with functional context, this review highlights conserved features and species-specific variations of arginine kinase that may inform the design of inhibitors. Such molecules have the potential to serve both as antiparasitic agents and as novel therapeutics to manage crustacean-related allergic responses in humans. Full article

Neglected diseases significantly impact the world, and there is a lack of effective treatments, requiring therapeutic alternatives. Thus, the study of the phytochemical and schistosomicidal activity evaluation of Copaifera oblongifolia leaves’ crude extract was conducted. The quercitrin (1) and afzelin (2) were isolated from the crude extract. In the in vitro schistosomicidal activity test, the isolated compounds demonstrated promising results, with 75% mortality at a concentration of 12.5 µM after 72 h. Molecular docking calculations indicated that compounds 1 and 2 could potentially interact with the amino acids of the FAD binding site in the TGR enzyme, a crucial enzyme for the survival of Schistosoma mansoni. These interactions could have binding energies comparable to praziquantel, a preferred drug for treating schistosomiasis. Therefore, in silico and in vitro investigations are crucial for developing new studies that can reveal the antiparasitic potential of compounds of plant origin. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Background/Objectives: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a major neglected tropical disease, with over six million cases concentrated, primarily in Latin America. Despite decades of research, treatment continues to rely on two outdated drugs—benznidazole and nifurtimox—both of which exhibit limited efficacy and are associated with severe side effects. In this context, drug repurposing presents a promising strategy to accelerate the development of safer and more effective therapies. Nitroxoline, a hydroxyquinoline compound widely used in Europe to treat bacterial urinary tract infections, has recently garnered attention for its broad-spectrum antimicrobial and anticancer activities. This study evaluated the antitrypanosomal potential of nitroxoline against both epimastigote and intracellular amastigote forms of T. cruzi, demonstrating significantly greater efficacy than benznidazole. Methods: In addition to its antiparasitic activity, we investigated the mechanism of parasite death and found that nitroxoline induces hallmarks of programmed cell death, including chromatin condensation, mitochondrial membrane depolarization, ATP depletion, reactive oxygen species accumulation, and increased membrane permeability. These cellular events are critical for minimizing host tissue inflammation and suggest a safer therapeutic profile. Results: The nitroxoline was shown to induce greater activity than the reference treatment, benznidazole, in addition to triggering events related to apoptotic or silent cell death. Conclusions: Given its established clinical use and favorable safety data, nitroxoline emerges as a strong candidate for further investigation as a repurposed treatment for Chagas disease. Future work should focus on in vivo efficacy, pharmacokinetics, and drug delivery strategies to enhance systemic bioavailability. Full article

Marine peptides, derived from a great number of aquatic organisms, exhibit a broad spectrum of biological activities that hold a significant therapeutic potential. This article reviews the multifaceted roles of marine peptides, focusing on their antibacterial, antibiofilm, antifungal, antiviral, antiparasitic, cytotoxic, anticancer, immunomodulatory, chemotactic, opsonizing, anti-inflammatory, antiaging, skin-protective, and wound-healing properties. By elucidating mechanisms of their action and highlighting key research findings, this review aims to provide a comprehensive understanding of possible therapeutic applications of marine peptides, underscoring their importance in developing novel drugs as well as in cosmetology, food industry, aquatic and agriculture biotechnology. Further investigations are essential to harness their therapeutic potential and should focus on detailed mechanism studies, large-scale production, and clinical evaluations with a view to confirm their efficacy and safety and translate these findings into practical applications. It is also important to investigate the potential synergistic effects of marine peptide combinations with existing medicines to enhance their efficacy. Challenges include the sustainable sourcing of marine peptides, and therefore an environmental impact of harvesting marine organisms must be considered as well. Full article

The ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) is a key target for the development of antiparasitic agents, particularly against ectoparasites, such as fleas and ticks. Binding stability and selectivity of sarolaner enantiomers for Ctenocephalides felis RDL receptors (RDLR) were investigated in the current study. Wild-type (WT) C. felis RDLR and its A285S mutant were constructed using homology-based, fragment-based threading and AI-driven approaches, of which, SWISS-MODEL generated the most reliable structures. Molecular docking showed that the sarolaner S-enantiomer had higher binding affinity for both receptors than the R-enantiomer, primarily due to hydrogen bonding with Ile256, π–π stacking with Phe326, and hydrophobic interactions with Ile267 and Ile268. Molecular dynamics simulations confirmed the binding stability of the S-enantiomer-receptor complex in which key residues maintained interactions throughout the trajectories. Binding free energy analysis supported these results and highlighted the role of nonpolar interactions in binding stability. The A285S mutation had minimal impact on the binding pocket, and the S-enantiomer remained selective for and bound to the mutant receptor. Insights into the insecticidal mechanism of sarolaner enantiomers are given, and the current findings may inform the development of veterinary drugs from novel isoxazoline-based NAMs targeting insect GABARs. Full article

Parasitic nematodes, such as the zoonotic rat lungworm Angiostrongylus cantonensis, pose a significant global health burden, with current anthelmintics like albendazole showing limited efficacy. Here, we report the isolation of piplartine from Piper truncatum Vell. (Piperaceae) and its potent in vitro activity against A. cantonensis larvae. Piplartine demonstrated superior efficacy to albendazole, with EC₅₀ values of 8.3 µM for first-stage larvae (L1) and 10.4 µM for infective third-stage larvae (L3), compared to 14.2 µM (L1) and 15.6 µM (L3) for albendazole. Notably, piplartine exhibited no toxicity in the Caenorhabditis elegans model at therapeutic concentrations, underscoring its selective antiparasitic action. In silico profiling further revealed favorable drug-likeness and pharmacokinetic properties, including high gastrointestinal absorption and blood–brain barrier permeability, which are critical for targeting neurotropic infections. As the first study to characterize the activity of piplartine against A. cantonensis, our work highlights its potential as a structurally novel anthelmintic lead. Based on the obtained results, piplartine may be considered a promising and accessible candidate for combating angiostrongyliasis and related helminthic infections. Full article

On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease 2019). There were neither drugs nor vaccines that were known to be effective against the virus, stimulating an urgent worldwide search for treatments. An evaluation of existing drugs by ‘repurposing’ was initiated followed by a transition to de novo drug discovery. Repurposing of an already approved drug may accelerate the introduction of that drug into clinical use by circumventing early, including preclinical studies otherwise essential for a de novo drug and reducing development costs. Early in the pandemic three drugs were identified as repurposing candidates for the treatment of COVID-19: (i) hydroxychloroquine, an anti-malarial also used to treat rheumatoid arthritis and lupus; (ii) ivermectin, an antiparasitic approved for both human and veterinary use; (iii) remdesivir, an anti-viral originally developed to treat hepatitis C. The scientific evidence, both for and against the efficacy of these three drugs as treatments for COVID-19, vied with public demand and politicization as unqualified opinions clashed with evidence-based medicine. To quote Hippocrates, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance”. Full article

Flavonoids and chalcones, widely recognised for their diverse biological activities, have garnered attention due to their potential therapeutic applications. This review discusses fluorinated flavonoids and chalcones, focusing on their prospective anti-inflammatory, antidiabetic, anticancer, antiosteoporotic, cardioprotective, neuroprotective, hepatoprotective, antimicrobial, and antiparasitic applications. The enhanced biological activities of fluorinated derivatives, particularly the antibacterial, antiviral, and anticancer properties, are attributed to the introduction of fluorine groups, which increase lipophilicity and metabolic stability. Key findings indicate that fluorinated flavonoids and chalcones exhibit synergistic effects with antibiotics, inhibit bacterial efflux pumps, and reveal potent antiviral and anticancer properties. However, challenges such as cytotoxicity and structural optimisation have to be addressed. The synthesis of fluorinated flavonoids and chalcones is discussed, with emphasis on various synthetic methods such as condensation and cyclisation reactions starting from fluorinated precursors, as well as fluorination strategies, including the use of molecular fluorine or fluorinating agents. Fluorinated flavonoids and chalcones represent candidates for therapeutic development and have the potential to overcome drug resistance. However, further studies are necessary to adjust their pharmacological profiles. Full article

Ivermectin (IVM) is a macrolide antiparasitic drug, and Metformin (MET) is a biguanide oral hypoglycemic drug. Studies have shown that both of them have obvious anti-tumor effects, but there have been no reports on the combined treatment of Canine breast tumors. This report aimed to investigate the effectiveness and the possible mechanism of drug combination on Canine breast cancers. Mouse breast tumor cells (4T1) and canine breast tumor cells (CMT-1211) were, respectively, treated with IVM, MET, and their combination, and then cell viability was assessed. After that, transcriptomic analysis was performed to study the action pathway of the drug combination with regard to its anti-tumor effects. Reactive oxygen species (ROS) levels were detected by flow cytometry, and autophagosome formation was observed by transmission electron microscopy (TEM). Immunofluorescence detected the cytoplasmic translocation of LC3B and P62 into the nucleus. Western blot detected the protein expressions of LC3B, P62, Beclin1, Bcl-2, p-PI3K, p-AKT, and p-mTOR. Our transcriptomic analysis showed that the combination of IVM and MET regulated the expression of autophagy-related genes and pathways, including the PI3K/AKT/mTOR signaling pathway. Our in vitro experiments showed that the combination of two drugs had a considerably significant effect on cytotoxicity, ROS levels, and the formation of autophagosomes compared to each drug alone. Meanwhile, the in vivo experiments showed that IVM combined with MET had an obvious inhibitory effect on tumor growth in canine breast tumor xenografts. This study concluded that IVM with MET activated autophagy, which killed breast cancer cells by inhibiting the activation of the PI3K/AKT/mTOR pathway and promoting the excessive accumulation of ROS. It offers a theoretical foundation for the synergistic effects of MET and IVM to suppress breast cancer cell activity. Full article

Objective: This study aimed to develop a robust multi-residue analytical method for the precise identification and quantification of six macrolide antiparasitic agents commonly used in animal husbandry feeds. Method: Feed samples were extracted using a water-saturated acetonitrile solution. The resulting crude extracts were then treated with n-hexane and further purified by HLB solid-phase extraction columns to obtain the test solutions. These prepared samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The method was validated across six different feed matrices, including pig premix, concentrate, and complete feed, as well as chicken premix, concentrate, and compound feed. The method exhibited average recoveries ranging from 80.07% to 98.80%. The intra-day coefficients of variation (CV) for the first three feed types ranged from 1.98% to 12.84%, while for the latter three, the CVs ranged from 2.43% to 13.69%. Results: The method’s precision led to the quantification limit of avermectin, doramectin, acetyl avermectin, and ivermectin being 25 μg/kg, whereas for moxifloxacin and milbemycin, the limit was 50 μg/kg. These thresholds meet the stringent requirements for trace drug analysis, supporting the method’s suitability for regulatory surveillance and monitoring of these specified antibiotics in animal feeds. Full article

Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide–alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases. Full article

Anthelmintic resistance is currently negatively impacting animal production parameters, leading to an increase in the prevalence of gastrointestinal nematodes and resulting in low profitability in small ruminants. Therefore, there is a need to develop alternative control strategies to reduce the prevalence and damage caused by these parasites in extensive systems. One of these strategies involves plant extracts and their secondary metabolites, which have shown antiparasitic properties. The main aim of the present study was the evaluation of Artemisia cina (A. cina) foliage to perform an n-hexane extract and cinaguaiacin as secondary metabolite (mixture of 63% of 3′-demethoxy-6-O-demethylisoguaiacin and 37% norisoguaiacin), previously identified by chromatography technique and relative expression of three antioxidant enzyme genes of infective Haemonchus contortus larvae (L₃). The results showed upregulation of glutathione peroxidase (GPx) and catalase (CAT), and decreased expression of superoxide dismutase (SOD) genes after exposure to H. contortus L₃ to n-hexane extract of A. cina. Furthermore, cinaguacin displayed up- and downregulation of GPx and superoxide dismutase genes, respectively. These data suggest the active function of reactive oxidative species (ROS) genes of H. contortus L₃ exposed by the extract of A. cina and cinaguaiacin to induce the larve death. In this sense, both alternatives could be promising to mitigate resistance to anthelmintic drugs. Full article

The serendipitous discovery of antiparasitic drugs, such as quinine and artemisinin, of plant origin reveals that searching new chemical pharmacophores from medicinal plants is valuable. The present study sought to explore the antiplasmodial, antileishmanial, and antitrypanosomal activities of Lippia adoensis extracts. Crude extracts of L. adoensis leaves and twigs, which were obtained by extraction using 70% ethanol in water, were assayed for antiplasmodial activity against P. falciparum 3D7 and Dd2 through the SYBR green I-based fluorescence assay; and for antileishmanial, antitrypanosomal, and cytotoxic effects on Leishmania donovani, Trypanosoma brucei brucei, and Vero cells, respectively, using resazurin colorimetric assays. In vitro phytochemical analysis of L. adoensis extracts was performed using standard methods. Moreover, liquid chromatography–mass spectrometry (LC-MS) feature-based detection and molecular networking flow on Global Natural Product Social (GNPS) were also used for the phytochemical screening of L. adoensis extracts. Crude extracts from L. adoensis inhibited the growth of P. falciparum (3D7 and Dd2) (IC₅₀s; (3D7): 10.00 and 97.46 μg/mL; (Dd2): 29.48 and 26.96 μg/mL), L. donovani (IC₅₀s: 22.87–10.52 μg/mL), and T. brucei brucei (IC₅₀s: 2.30–55.06 μg/mL). The extracts were found to be non-cytotoxic to Vero cells, thus yielding median cytotoxic concentrations (CC₅₀s) above 100 μg/mL. In vitro phytochemical analysis of the crude extracts revealed the presence of alkaloids, terpenoids, phenolic compounds, and carbohydrates. The LC-MS tandem molecular networking flow predicted that the extracts contained valsafungin A and bacillamidin in the first cluster, and fatty acids, ketone, and aldehyde derivatives in the second cluster. Overall, the present study demonstrated the antiparasitic effects of L. adoensis extracts, thus justifying the use of this plant in the traditional treatment of fever and malaria conditions. Nevertheless, detailed metabolomic studies and antiparasitic mechanisms of action of the extracts are expected to unveil the potential antiparasitic hit compounds. Full article