Tephrosia toxicaria (Sw.) Pers. extracts: Screening by examining aedicidal action under laboratory and field conditions along with its antioxidant, antileishmanial, and antimicrobial activities.

An increase in the incidence of arboviral, microbial and parasitic infections, and to disorders related to oxidative stress has encouraged the development of adjuvant therapies based on natural formulations, such as those involving plant extracts. Thus, to expand the repertoire of the available therapeutic options, this study aimed to describe the versatility of Tephrosia toxicaria (Sw.) (Pers., 1807) extracts for the control of arbovirus vectors, as well as their antioxidant, antileishmanial, and antimicrobial potential. Among the aqueous and hydroethanolic extracts obtained, the hydroethanolic extract from roots (RHA) was identified as the most active larvicide extract demonstrating, respectively, the lowest lethal concentration (mg/mL) for 50%, 90% and 99% of Aedes aegypti (L., 1762) and Aedes albopictus (S., 1894) larvae, observed at 24 h (0.33, 0.84 and 1.80; 0.32, 0.70 and 1.32) and 48 h (0.17, 0.51 and 1.22; 0.26, 0.47 and 0.78) post-exposure. Field assays revealed that RHA (0.84 mg/mL) is a potential oviposition deterrent, reducing egg-laying by approximately 90%. RHA (0.1 mg/mL) also exhibited antioxidant activity for the following tests: total antioxidant capacity (286.86 mg AAE/g), iron (87.16%) and copper (25.64%) chelation, and superoxide scavenging (10%). In the cell culture assays, RHA (0.1 mg/mL) promoted regeneration of metabolic activity (92% cell viability) in cells exposed to oxidative stress. Furthermore, RHA displayed weak antileishmanial activity (IC50 = 3.53 mg/mL) against Leishmania amazonensis and not exhibit antimicrobial activity. The extraction favored the concentration of carbohydrates in RHA, in addition to lectins and protease inhibitors, with molecular masses estimated between 10 and 24 kDa. Cytotoxicity and phytotoxicity analyses of RHA suggested its biosecurity. Thus, RHA is a multivalent extract with insecticide and antioxidant properties at low and safe concentrations. However, others studies on its indirect toxic effects are ongoing to ensure the complete safety of RHA.

pH-responsive phthalate cashew gum nanoparticles for improving drugs delivery and anti-Trypanosoma cruzi efficacy.

Nanotechnology is a crucial technology in recent years has resulted in new and creative applications of nanomedicine. Polymeric nanoparticles have increasing demands in pharmaceutical applications and require high reproducibility, homogeneity, and control over their properties. Work explores the use of cashew phthalate gum (PCG) as a particle-forming polymer. PCG exhibited a pH-sensitive behavior due to the of acid groups on its chains, and control drug release. We report the development of nanoparticles carrying benznidazole. Formulations were characterized by DLS, encapsulation efficiency, drug loading, FTIR, pH-responsive behavior, release, and in vitro kinetics. Interaction between polymer and drug was an evaluated by molecular dynamics. Morphology was observed by SEM, and in vitro cytotoxicity by MTT assay. Trypanocidal effect for epimastigote and trypomastigote forms was also evaluated. NPs responded to the slightly basic pH, triggering the release of BNZ. In acidic medium, they presented small size, spherical shape, and good stability. It was indicated NP with enhanced biological activity, reduced cytotoxicity, high anti T. cruzi performance, and pH-sensitive release. This work investigated properties related to the development and enhancement of nanoparticles. PCG has specific physicochemical properties that make it a promising alternative to drug delivery, however, there are still challenges to be overcome.

Silver Nanoparticles Containing Fucoidan Synthesized by Green Method Have Anti-Trypanosoma cruzi Activity.

The brown seaweed Spatoglossum schröederi synthesizes three bioactive fucoidans, the most abundant of which is fucan A. This fucoidan was extracted and its identity was confirmed by chemical analysis, Fourier-transform infrared spectroscopy (FTIR), and agarose gel electrophoresis. Thereafter, silver nanoparticles containing fucan A (AgFuc) were produced using an environmentally friendly synthesis method. AgFuc synthesis was analyzed via UV-vis spectroscopy and FTIR, which confirmed the presence of both silver and fucan A in the AgFuc product. Dynamic light scattering (DLS), X-ray diffraction, scanning electron microscopy, and atomic force microscopy revealed that the AgFuc particles were ~180.0 nm in size and spherical in shape. DLS further demonstrated that AgFuc was stable for five months. Coupled plasma optical emission spectrometry showed that the AgFuc particles contained 5% silver and 95% sugar. AgFuc was shown to be more effective in inhibiting the ability of parasites to reduce MTT than fucan A or silver, regardless of treatment time. In addition, AgFuc induced the death of ~60% of parasites by necrosis and ~17% by apoptosis. Therefore, AgFuc induces damage to the parasites' mitochondria, which suggests that it is an anti-Trypanosoma cruzi agent. This is the first study to analyze silver nanoparticles containing fucan as an anti-Trypanosoma cruzi agent. Our data indicate that AgFuc nanoparticles have potential therapeutic applications, which should be determined via preclinical in vitro and in vivo studies.

VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases.

Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by Trypanosoma cruzi, Leishmania spp., and Trypanosoma brucei. In this context, it is important to consider the evasion mechanisms of these protozoa in the host and the antigens involved in the mechanisms of the parasite-host interaction. Thus, the immunostimulatory properties of VLPs can be part of an important strategy for the development and evaluation of new vaccines. This work aims to highlight the potential of VLPs as vaccine adjuvants for the development of immunity in complex diseases, specifically in the context of tropical diseases caused by trypanosomatids.

Antimicrobial Activity of Chitosan Oligosaccharides with Special Attention to Antiparasitic Potential.

The global rise of infectious disease outbreaks and the progression of microbial resistance reinforce the importance of researching new biomolecules. Obtained from the hydrolysis of chitosan, chitooligosaccharides (COSs) have demonstrated several biological properties, including antimicrobial, and greater advantage over chitosan due to their higher solubility and lower viscosity. Despite the evidence of the biotechnological potential of COSs, their effects on trypanosomatids are still scarce. The objectives of this study were the enzymatic production, characterization, and in vitro evaluation of the cytotoxic, antibacterial, antifungal, and antiparasitic effects of COSs. NMR and mass spectrometry analyses indicated the presence of a mixture with 81% deacetylated COS and acetylated hexamers. COSs demonstrated no evidence of cytotoxicity upon 2 mg/mL. In addition, COSs showed interesting activity against bacteria and yeasts and a time-dependent parasitic inhibition. Scanning electron microscopy images indicated a parasite aggregation ability of COSs. Thus, the broad biological effect of COSs makes them a promising molecule for the biomedical industry.

Novel Solid Dispersions of Naphthoquinone Using Different Polymers for Improvement of Antichagasic Activity.

IVS320 (3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione) is a naphthoquinone that has low solubility in aqueous medium, a physical behavior that limits its biological activities, considering that compounds from this class have several activities. In this work, solid dispersions (SDs) prepared between IVS320 and polymers hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP) were developed using physical mixture (PM), kneading (KN), and rotary evaporation (RE) methods. Dispersions were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). In addition, in vitro antiparasitic activity in Trypanosoma cruzi Y strains was evaluated. Physical-chemical characterization demonstrated the formation of SDs through the interaction of IVS320 with polymeric matrices. SDs of IVS320-polymer presented a significant potentiation of antichagasic activity, with inhibitory growth around 62% (IVS320-HPMC/RE), 55% (IVS320-PEG/RE), and 85% (IVS320-PVP/RE), while pure IVS320 showed a value of 48% for the highest concentrations evaluated (50 µg/mL).

Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological.

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.