Catechol compounds as dual-targeting agents for fish protection against Ichthyophthirius multifiliis infections.

Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.

Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile.

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound 26/HIT 8. We previously identified this molecule as a 'hit' during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position. Compounds were assessed in vitro to identify their cytotoxicity properties. Of note, several compounds in the series displayed relevant cytotoxicity, which warrants scrutiny while interpreting biological activities that have been reported for structurally related molecules. In addition, antiparasitic activities were recorded against a range of human-infective protozoa, including Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania infantum. The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.

Therapeutic Potential of Marine-Derived Cyclic Peptides as Antiparasitic Agents.

Parasitic diseases still compromise human health. Some of the currently available therapeutic drugs have limitations considering their adverse effects, questionable efficacy, and long treatment, which have encouraged drug resistance. There is an urgent need to find new, safe, effective, and affordable antiparasitic drugs. Marine-derived cyclic peptides have been increasingly screened as candidates for developing new drugs. Therefore, in this review, a systematic analysis of the scientific literature was performed and 25 marine-derived cyclic peptides with antiparasitic activity (1-25) were found. Antimalarial activity is the most reported (51%), followed by antileishmanial (27%) and antitrypanosomal (20%) activities. Some compounds showed promising antiparasitic activity at the nM scale, being active against various parasites. The mechanisms of action and targets for some of the compounds have been investigated, revealing different strategies against parasites.

Antiparasitic activity of ivermectin: Four decades of research into a "wonder drug".

Parasitic diseases still pose a serious threat to human and animal health, particularly for millions of people and their livelihoods in low-income countries. Therefore, research into the development of effective antiparasitic drugs remains a priority. Ivermectin, a sixteen-membered macrocyclic lactone, exhibits a broad spectrum of antiparasitic activities, which, combined with its low toxicity, has allowed the drug to be widely used in the treatment of parasitic diseases affecting humans and animals. In addition to its licensed use against river blindness and strongyloidiasis in humans, and against roundworm and arthropod infestations in animals, ivermectin is also used "off-label" to treat many other worm-related parasitic diseases, particularly in domestic animals. In addition, several experimental studies indicate that ivermectin displays also potent activity against viruses, bacteria, protozoans, trematodes, and insects. This review article summarizes the last 40 years of research on the antiparasitic effects of ivermectin, and the use of the drug in the treatment of parasitic diseases in humans and animals.

First-Row Transition 7-Oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes: Antiparasitic Activity and Release Studies.

Leishmaniasis and Chagas disease are still considered neglected illnesses due to the lack of investment in research, despite the fact that almost one million new cases are reported every year. Four 7-oxo-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidine (HftpO) first-row transition complexes (Cu, Co, Ni, Zn) have been studied for the first time in vitro against five different species of Leishmania spp. (L. infantum, L. braziliensis, L. donovani, L. peruviana and L. mexicana) as well as Trypanosoma cruzi, showing higher efficacy than the reference commercial drugs. UV and luminescence properties were also evaluated. As a proof of concept, anchoring of a model high-effective-metal complex as an antiparasitic agent on silica nanoparticles was carried out for the first time, and drug-release behaviour was evaluated, assessing this new approach for drug vehiculation.

Synthesis, characterization, and antiparasitic effects of zinc oxide nanoparticles-eugenol nanosuspension against Toxoplasma gondii infection.

Background: In this study, zinc oxide nanoparticles-coated with eugenol (ZnO@Eug) were synthesized and evaluated as a nanosuspension (NSus) formulation against Toxoplasma gondii in vitro and in vivo. Methods: An anti-Toxoplasma activity assay for ZnO@Eug NSus was conducted in vitro, ex vivo, and in vivo. FTIR spectroscopy confirmed the formation of ZnO@Eug NSus by detecting several functional groups involved; EDX and SEM demonstrated the grain of ZnO-NPs embedded with Eug and compositional purity. Results: Surface charge (ZP) and size distribution (DLS) of ZnO@Eug NSus were determined to be -22.7 mV and 109.6 nm, respectively. According to the release kinetics, approximately 60% of the ZnO-NPs and Eug were released in the first 45 min. In the cytotoxicity assay, ZnO-NPs, Eug, and ZnO@Eug NSus had IC50 values of 71.85, 22.39, and 2.02 mg/mL, respectively. The therapeutic efficacy of ZnO@Eug against T. gondii was 56.3%, which was not significantly different from that of spiramycin (58.9%) (Positive-control). The tissue tachyzoites in the liver, spleen, and peritoneum were less than 50% in groups treated with Eug, spiramycin, and ZnO@Eug NSus compared to the control. ZnO@Eug-treated groups showed a survival rate of up to 13 days. Conclusions: The ZnO@Eug NSus demonstrated antiparasitic activity against T. gondii with minimal toxic effects and high efficiency in increasing the survival of infected mice. The nanoformulations of ZnO-NPs incorporated with Eug could, in the future, be considered for treating toxoplasmosis in humans and animals if a detailed study was conducted to determine the precise dose and measure side effects.

In vitro studies for antiparasitic activities of Punica granatum extract.

Because of the drug resistance, medicinal plants are used more frequently than coccidiostats to treat and control coccidiosis. Punica granatum is a powerful antioxidant with a variety of medicinal uses. This study used an in vitro experiment to investigate how different P. granatum from Yemen (Y) and Egypt (E) sources affected oocyst sporulation and served as an anthelminthic effector. In contrast to PGE and mebendazole, PGY (200 mg/mL) has the shortest time to paralyze and death the earthworm Eisenia fetida in this investigation. In addition, the treated worm groups' cuticle thickness and shrinkage in comparison to the control group were assessed and contrasted. Eimeria papillata is used as a model protozoan parasite in anticoccidial assays. This study shows that P. granatum affects oocysts sporulation in a dose-dependent manner, with maximal percentages of 100% (PGY) and 48.60% (PGE) at 96 h for P. granatum concentrations of 200 mg/mL. Inhibition (%) was compared to various detergents, as well as positive and negative controls. According to our research, the P. granatum extract had powerful anthelmintic and anticoccidial properties, with the potency changing according to the environmental conditions of each fruit source. RESEARCH HIGHLIGHTS: Habitat of the plant is useful for production and accumulation of some secondary metabolites in plants which be effective for the therapeutic uses. Different parameters in the environmental ecosystem affecting variation in chemical compositions and biological activity of P. granatum.

Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome.

Bismuth-based drugs have been used primarily to treat ulcers caused by Helicobacter pylori and other gastrointestinal ailments. Combined with antibiotics, these drugs also possess synergistic activity, making them ideal for multiple therapy regimens and overcoming bacterial resistance. Compounds based on bismuth have a low cost, are safe for human use, and some of them are also effective against tumoral cells, leishmaniasis, fungi, and viruses. However, these compounds have limited bioavailability in physiological environments. As a result, there is a growing interest in developing new bismuth compounds and approaches to overcome this challenge. Considering the beneficial properties of bismuth and the importance of discovering new drugs, this review focused on the last decade's updates involving bismuth compounds, especially those with potent activity and low toxicity, desirable characteristics for developing new drugs. In addition, bismuth-based compounds with dual activity were also highlighted, as well as their modes of action and structure-activity relationship, among other relevant discoveries. In this way, we hope this review provides a fertile ground for rationalizing new bismuth-based drugs.

Antiplasmodial, Trypanocidal, and Genotoxicity In Vitro Assessment of New Hybrid α,α-Difluorophenylacetamide-statin Derivatives.

BACKGROUND: Statins present a plethora of pleiotropic effects including anti-inflammatory and antimicrobial responses. A,α-difluorophenylacetamides, analogs of diclofenac, are potent pre-clinical anti-inflammatory non-steroidal drugs. Molecular hybridization based on the combination of pharmacophoric moieties has emerged as a strategy for the development of new candidates aiming to obtain multitarget ligands. METHODS: Considering the anti-inflammatory activity of phenylacetamides and the potential microbicidal action of statins against obligate intracellular parasites, the objective of this work was to synthesize eight new hybrid compounds of α,α-difluorophenylacetamides with the moiety of statins and assess their phenotypic activity against in vitro models of Plasmodium falciparum and Trypanosoma cruzi infection besides exploring their genotoxicity safety profile. RESULTS: None of the sodium salt compounds presented antiparasitic activity and two acetated compounds displayed mild anti-P. falciparum effect. Against T. cruzi, the acetate halogenated hybrids showed moderate effect against both parasite forms relevant for human infection. Despite the considerable trypanosomicidal activity, the brominated compound revealed a genotoxic profile impairing future in vivo testing. CONCLUSIONS: However, the chlorinated derivative was the most promising compound with chemical and biological profitable characteristics, without presenting genotoxicity in vitro, being eligible for further in vivo experiments.

Valorizing Constituents of Cashew Nut Shell Liquid toward the Sustainable Development of New Drugs against Chagas Disease.

Six new ether phospholipid analogues encompassing constituents from cashew nut shell liquid as the lipid portion were synthesized in an effort to valorize byproducts of the cashew industry toward the generation of potent compounds against Chagas disease. Anacardic acids, cardanols, and cardols were used as the lipid portions and choline as the polar headgroup. The compounds were evaluated for their in vitro antiparasitic activity against different developmental stages of Trypanosoma cruzi. Compounds 16 and 17 were found to be the most potent against T. cruzi epimastigotes, trypomastigotes, and intracellular amastigotes exhibiting selectivity indices against the latter 32-fold and 7-fold higher than current drug benznidazole, respectively. Hence, four out of six analogues can be considered as hit-compounds toward the sustainable development of new treatments for Chagas disease, based on inexpensive agro-waste material.

Piplartine-Inspired 3,4,5-Trimethoxycinnamates: Trypanocidal, Mechanism of Action, and In Silico Evaluation.

Chagas disease (CD) is one of the main neglected tropical diseases that promote relevant socioeconomic impacts in several countries. The therapeutic options for the treatment of CD are limited, and parasite resistance has been reported. Piplartine is a phenylpropanoid imide that has diverse biological activities, including trypanocidal action. Thus, the objective of the present work was to prepare a collection of thirteen esters analogous to piplartine (1-13) and evaluate their trypanocidal activity against Trypanosoma cruzi. Of the tested analogues, compound 11 ((E)-furan-2-ylmethyl 3-(3,4,5-trimethoxyphenyl)acrylate) showed good activity with IC50 values = 28.21 ± 5.34 µM and 47.02 ± 8.70 µM, against the epimastigote and trypomastigote forms, respectively. In addition, it showed a high rate of selectivity to the parasite. The trypanocidal mechanism of action occurs through the induction of oxidative stress and mitochondrial damage. In addition, scanning electron microscopy showed the formation of pores and leakage of cytoplasmic content. Molecular docking indicated that 11 probably produces a trypanocidal effect through a multi-target mechanism, including affinity with proteins CRK1, MPK13, GSK3B, AKR, UCE-1, and UCE-2, which are important for the survival of the parasite. Therefore, the results suggest chemical characteristics that can serve for the development of new trypanocidal prototypes for researching drugs against Chagas disease.

Synthesis and biological evaluation of carbohydrate-Coumarin/vanillic acid hybrid as a promising antiparasitic agent.

Leishmaniasis is caused by infection with the protozoan parasites Leishmania. It is classified as one of the most significant neglected tropical diseases. It remains a significant global public health concern. Current treatments include the use of pentavalent antimonial, amphotericin B, pentamidine, miltefosine, and paromomycin. However, several limitations such as toxicity, side effect, and resistance to these drugs of certain species are of concern. To combat this disease, effective chemotherapy is urgently required for its treatment and management. In this study, we synthesized a series of carbohydrate-coumarin/vanillic acid hybrids linked through triazole moiety via CuACC (Copper-catalysed azide-alkyne cycloaddition) reaction. These compounds were evaluated for their in vitro antiparasitic activity using MTT assay against Leishmania donovani whereas, all compounds show IC50 value in the range of 65-74 µM.

Alkaline oxidization can increase the in vitro antiparasitic activity of proanthocyanidin-rich plant extracts against Ascarissuum.

Proanthocyanidins (PAs) are a class of plant specialized metabolites with well-documented bioactivities such as antiparasitic effects. However, little is known about how the modification of PAs influences their bioactivity. The objective of this study was to investigate a wide range of PA-containing plant samples to determine if extracts containing PAs modified by oxidation had altered antiparasitic activities, compared to the original extracts that had not been modified in alkaline conditions. We extracted and analyzed samples from 61 proanthocyanidin-rich plants. The extracts were then oxidized under alkaline conditions. We used these non-oxidized and oxidized proanthocyanidin-rich extracts to conduct a detailed analysis of direct antiparasitic effects against the intestinal parasite Ascaris suum in vitro. These tests showed that the proanthocyanidin-rich extracts had antiparasitic activity. Modification of these extracts significantly increased the antiparasitic activity for the majority the extracts, suggesting that the oxidation procedure enhanced the bioactivity of the samples. Some samples that showed no antiparasitic activity before oxidation showed very high activity after the oxidation. High levels of other polyphenols in the extracts, such as flavonoids, was found to be associated with increased antiparasitic activity following oxidation. Thus, our in vitro screening opens up the opportunity for future research to better understand the mechanism of action how alkaline treatment of PA-rich plant extracts increases their biological activity and potential as novel anthelmintics.

Antileishmanial Activity of Cinnamic Acid Derivatives against Leishmania infantum.

Leishmania infantum is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. L. infantum is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against L. infantum is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound 32 (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC50 = 33.71 µM) with the highest selectivity index (SI > 42.46), followed by compound 15 (piperonyl cinnamate) with an IC50 = 42.80 µM and SI > 32.86. Compound 32 was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in L. infantum was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against Leishmania species.

In Vitro Evaluation of Antiprotozoal Properties, Cytotoxicity Effect and Anticancer Activity of New Essential-Oil Based Phytoncide Mixtures.

Protozoa, in both humans and animals, are one of the leading causes of disease. International programmes introduced in many countries have helped reduce the incidence of disease. However, it has recently become increasingly difficult to achieve the goals set for the coming years. One of the main reasons for this, as with other pathogenic organisms, such as bacteria and fungi, is the increasing resistance to current methods of treating and preventing infection. Therefore, new therapies with high efficacy are needed. In the present study, the novel mixtures of essential oils (EOs), clove, garlic, Ceylon cinnamon, and rosemary with organic acids (acetic, propionic, lactic) and metal ions (Cu, Mn, Zn) were tested against five selected model protozoa (Euglena gracilis, Gregarina blattarum, Amoeba proteus, Paramecium caudatum, Pentatrichomonas hominis). The cytotoxicity and potential anticancer activity of the obtained combinations were tested on the human fibroblasts (NHDF) and human cancer cell lines (A549, MCF7, LoVo, HT29). All of the mixtures showed very good antiprotozoal properties. The most efficient were the combination of clove and rosemary essential oils, mixtures of acids, and Mn ions. The LD50 values were in the range of 0.001-0.006% and the LD100 values were 0.002-0.008%. All of the tested mixtures did not show cytotoxicity against normal cells, but did show growth inhibition against cancer cell lines. The most cytotoxic against cancer cells were combinations with cinnamon essential oil. Nevertheless, the proposed combinations containing essential oils, organic acids, and metal ions have high antiprotozoal activity, with low toxicity to healthy human cells.

Antimicrobial Spectrum of Activity and Mechanism of Action of Linear Alpha-Helical Peptides Inspired by Shrimp Anti-Lipopolysaccharide Factors.

Shrimp antilipopolysaccharide factors (ALFs) form a multifunctional and diverse family of antimicrobial host defense peptides (AMPs) composed of seven members (groups A to G), which differ in terms of their primary structure and biochemical properties. They are amphipathic peptides with two conserved cysteine residues stabilizing a central ß-hairpin that is understood to be the core region for their biological activities. In this study, we synthetized three linear (cysteine-free) peptides based on the amino acid sequence of the central ß-hairpin of the newly identified shrimp (Litopenaeus vannamei) ALFs from groups E to G. Unlike whole mature ALFs, the ALF-derived peptides exhibited an α-helix secondary structure. In vitro assays revealed that the synthetic peptides display a broad spectrum of activity against both Gram-positive and Gram-negative bacteria and fungi but not against the protozoan parasites Trypanosoma cruzi and Leishmania (L.) infantum. Remarkably, they displayed synergistic effects and showed the ability to permeabilize bacterial membranes, a mechanism of action of classical AMPs. Having shown low cytotoxicity to THP-1 human cells and being active against clinical multiresistant bacterial isolates, these nature-inspired peptides represent an interesting class of bioactive molecules with biotechnological potential for the development of novel therapeutics in medical sciences.

Structure-activity relationship of dibenzylideneacetone analogs against the neglected disease pathogen, Trypanosoma brucei.

Trypanosoma brucei is a protozoan parasite that causes Human African Trypanosomiasis (HAT), a neglected tropical disease (NTD) that is endemic in 36 countries in sub-Saharan Africa. Only a handful drugs are available for treatment, and these have limitations, including toxicity and drug resistance. Using the natural product, curcumin, as a starting point, several curcuminoids and related analogs were evaluated against bloodstream forms of T. b. brucei. A particular subset of dibenzylideneacetone (DBA) compounds exhibited potent in vitro antitrypanosomal activity with sub-micromolar EC50 values. A structure-activity relationship study including 26 DBA analogs was initiated, and several compounds exhibited EC50 values as low as 200 nM. Cytotoxicity counter screens in HEK293 cells identified several compounds having selectivity indices above 10. These data suggest that DBAs offer starting points for a new small molecule therapy of HAT.

A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling Using Leishmania donovani.

Metals have been used in medicine since ancient times for the treatment of different ailments with various elements such as iron, gold and arsenic. Metal complexes have also been reported to show antibiotic and antiparasitic activity. In this context, we tested the antiparasitic potential of 10 organotin (IV) derivatives from 4-(4-methoxyphenylamino)-4 oxobutanoic acid (MS26) against seven eukaryotic pathogens of medical importance: Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Entamoeba histolytica, Giardia lamblia, Naegleria fowleri and Schistosoma mansoni. Among the compounds with and without antiparasitic activity, compound MS26Et3 stood out with a 50% effective concentration (EC50) of 0.21 and 0.19 µM against promastigotes and intracellular amastigotes of L. donovani, respectively, 0.24 µM against intracellular amastigotes of T. cruzi, 0.09 µM against T. brucei, 1.4 µM against N. fowleri and impaired adult S. mansoni viability at 1.25 µM. In terms of host/pathogen selectivity, MS26Et3 demonstrated relatively mild cytotoxicity toward host cells with a 50% viability concentration of 4.87 µM against B10R cells (mouse monocyte cell line), 2.79 µM against C2C12 cells (mouse myoblast cell line) and 1.24 µM against HEK923 cells (human embryonic kidney cell line). The selectivity index supports this molecule as a therapeutic starting point for a broad spectrum antiparasitic alternative. Proteomic analysis of host cells infected with L. donovani after exposure to MS26Et3 showed a reduced expression of Rab7, which may affect the fusion of the endosome with the lysosome, and, consequently, impairing the differentiation of L. donovani to the amastigote form. Future studies to investigate the molecular target(s) and mechanism of action of MS26Et3 will support its chemical optimization.

Amoebicidal and trichomonicidal capacity of polymeric nanoparticles loaded with extracts of the plants Curcuma longa (Zingiberaceae) and Berberis vulgaris (Berberidaceae) / Capacidad amebicida y tricomonicida de nanopartículas poliméricas cargadas con extractos de las plantas Curcuma longa (Zingiberaceae) y Berberis vulgaris (Berberidaceae)

Abstract Introduction: Pathogenic protozoans, like Entamoeba histolytica and Trichomonas vaginalis, represent a major health problem in tropical countries; and polymeric nanoparticles could be used to apply plant extracts against those parasites. Objective: To test Curcuma longa ethanolic extract and Berberis vulgaris methanolic extracts, and their main constituents, against two species of protozoans. Methods: We tested the extracts, as well as their main constituents, curcumin (Cur) and berberine (Ber), both non-encapsulated and encapsulated in polymeric nanoparticles (NPs), in vitro. We also determined nanoparticle characteristics by photon correlation spectroscopy and scanning electron microscopy, and hemolytic capacity by hemolysis in healthy erythrocytes. Results: C. longa consisted mainly of tannins, phenols, and flavonoids; and B. vulgaris in alkaloids. Encapsulated particles were more effective (P < 0.001); however, curcumin and berberine nanoparticles were the most effective treatments. CurNPs had IC50 values (µg/mL) of 9.48 and 4.25, against E. histolytica and T. vaginalis, respectively, and BerNPs 0.24 and 0.71. The particle size and encapsulation percentage for CurNPs and BerNPs were 66.5 and 73.4 nm, and 83.59 and 76.48 %, respectively. The NPs were spherical and significantly reduced hemolysis when compared to non-encapsulated extracts. Conclusions: NPs represent a useful and novel bioactive compound delivery system for therapy in diseases caused by protozoans.

Resumen Introducción: Los protozoos patógenos, como Entamoeba histolytica y Trichomonas vaginalis, representan un importante problema de salud en los países tropicales; y se podrían usar nanopartículas poliméricas para aplicar extractos de plantas contra esos parásitos. Objetivo: Probar los extractos etanólicos de Curcuma longa y Berberis vulgaris, y sus principales constituyentes, contra dos especies de protozoos. Métodos: Probamos los extractos, así como sus principales constituyentes, curcumina (Cur) y berberina (Ber), tanto no encapsulados como encapsulados en nanopartículas poliméricas (NPs), in vitro. También determinamos las características de las nanopartículas por espectroscopía de correlación de fotones y microscopía electrónica de barrido, y la capacidad hemolítica por hemólisis en eritrocitos sanos. Resultados: C. longa tenía principalmente: taninos, fenoles y flavonoides; y B. vulgaris, alcaloides. Las partículas encapsuladas fueron más efectivas (P < 0.001); sin embargo, las nanopartículas de curcumina y berberina fueron los tratamientos más efectivos. CurNPs tenía valores IC50 (µg/mL) de 9.48 y 4.25, contra E. histolytica y T. vaginalis, respectivamente, y BerNPs 0.24 y 0.71. El tamaño de partícula y el porcentaje de encapsulación para CurNPs y BerNPs fueron: 66.5 y 73.4 nm, y 83.59 y 76.48 %, respectivamente. Los NP son esféricos y redujeron significativamente la hemólisis en comparación con los extractos no encapsulados. Conclusiones: Las NP representan un sistema de administración de compuestos bioactivos útil y novedoso para la terapia enfermedades causadas por protozoos.

Synthesis, Photophysical Properties and Biological Evaluation of New Conjugates BODIPY: Dinuclear Trithiolato-Bridged Ruthenium(II)-Arene Complexes.

The synthesis, photophysical properties and antiparasitic efficacy against Toxoplasma gondii ß-gal (RH strain tachyzoites expressing ß-galactosidase) grown in human foreskin fibroblast monolayers (HFF) of a series of 15 new conjugates BODIPY-trithiolato-bridged dinuclear ruthenium(II)-arene complexes are reported (BODIPY=4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, derivatives used as fluorescent markers). The influence of the bond type (amide vs. ester), as well as that of the length and nature (alkyl vs. aryl) of the spacer between the dye and the diruthenium(II) complex moiety, on fluorescence and biological activity were evaluated. The assessed photophysical properties revealed that despite an important fluorescence quenching effect observed after conjugating the BODIPY to the diruthenium unit, the hybrids could nevertheless be used as fluorescent tracers. Although the antiparasitic activity of this series of conjugates appears limited, the compounds demonstrate potential as fluorescent probes for investigating the intracellular trafficking of trithiolato-bridged dinuclear Ru(II)-arene complexes in vitro.