The present study consists of a detailed phylogenetic analysis of myxosporeans of the Myxobolus and Henneguya genera, including sequences from 12 Myxobolus/Henneguya species, parasites of South ...American pimelodids, bryconids and characids. Maximum likelihood and maximum parsimony analyses, based on 18 S rDNA gene sequences, showed that the strongest evolutionary signal is the phylogenetic affinity of the fish hosts, with clustering mainly occurring according to the order and/or family of the host. Of the 12 South American species studied here, six are newly described infecting fish from the Brazilian Pantanal wetland. Henneguya maculosus n. sp. and Myxobolus flavus n. sp. were found infecting both Pseudoplatystoma corruscans and Pseudoplatystoma reticulatum; Myxobolus aureus n. sp. and Myxobolus pantanalis n. sp. were observed parasitizing Salminus brasiliensis and Myxobolus umidus n. sp. and Myxobolus piraputangae n. sp. were detected infecting Brycon hilarii.
Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite
The current treatment (benznidazole and nifurtimox) is unsatisfactory, and ...potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of
The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other
strains and in combination with other drugs.
The search of new antioxidants, as drugs candidates, is an active field of medicinal chemistry. The synthesis of compounds with antioxidant potential has increased in recent years and a high number ...of structurally diverse compounds have been published. This review aims to show the current state-of-the-art on the development of antioxidant compounds incorporating the pyrazole pharmacophore. It is a well-timed review driven by the increasing number of papers, on this issue, that have been published since the beginning of the 21st century (from 2000 to 2017). The aim is to look deeper into the structures already published in the literature containing the pyrazole core as the unique pharmacophore or combined with other pharmacophores and see the relationship between the presence of this five-membered nitrogen heterocycle and the behaviour of the compounds as potential antioxidant agents. An attempt was made to whenever possible establish structure-activity relationships that could help the design of new and more potent antioxidant agents containing this important pharmacophore.
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•Pyrazole is an important pharmacophore in the development of antioxidants.•Pyrazoles alone or combined with other pharmacophores showed high antioxidant activity.•Hybridization with known antioxidants can be a strategy to increase pyrazoles activity.•Important structure-activity relationships were disclosed and presented herein.
There is a growing interest in controlling the synthesis of colloidal metal nanocrystals and thus tailoring their properties toward various applications. In this context, choosing an appropriate ...combination of reagents (e.g., salt precursor, reductant, capping agent, and stabilizer) plays a pivotal role in enabling the synthesis of metal nanocrystals with diversified sizes, shapes, and structures. Here we present a comprehensive review that highlights one of the key reagents for the synthesis of metal nanocrystals via chemical reduction: the reductants. We start with a brief introduction to the compounds commonly employed as reductants in the colloidal synthesis of metal nanocrystals by showing their oxidation half‐reactions and the corresponding oxidation potentials. Then we offer specific examples pertaining to the controlled synthesis of metal nanocrystals, followed by some fundamental aspects covering the general mechanisms of metal ion reduction based on the Marcus Theory. Afterwards, we present a case‐by‐case discussion on a wide variety of reductants, including their major properties, reduction mechanisms, and additional effects on the final products. We illustrate these aspects by selecting key examples from the literature and paying close attention to the underlying mechanism in each case. At the end, we conclude by summarizing the highlights of the review and providing some perspectives on future directions.
Reductants play a pivotal role in controlling the shapes and surface structures of noble‐metal nanocrystals, which affect both the reaction kinetics and thermodynamics significantly. By choosing an appropriate reductant, one is able to produce various noble metal nanocrystals with a variety of shapes, with typical examples including Pd, Pt, Au, Ag, and Rh.
Tauopathies are neurodegenerative diseases characterized by the pathological accumulation of microtubule-associated protein tau (MAPT) in the form of neurofibrillary tangles and paired helical ...filaments in neurons and glia, leading to brain cell death. These diseases include frontotemporal dementia (FTD) and Alzheimer's disease (AD) and can be sporadic or inherited when caused by mutations in the
gene. Despite an incredibly high socio-economic burden worldwide, there are still no effective disease-modifying therapies, and few tau-focused experimental drugs have reached clinical trials. One major hindrance for therapeutic development is the knowledge gap in molecular mechanisms of tau-mediated neuronal toxicity and death. For the promise of precision medicine for brain disorders to be fulfilled, it is necessary to integrate known genetic causes of disease, i.e.,
mutations, with an understanding of the dysregulated molecular pathways that constitute potential therapeutic targets. Here, the growing understanding of known and proposed mechanisms of disease etiology will be reviewed, together with promising experimental tau-directed therapeutics, such as recently developed tau degraders. Current challenges faced by the fields of tau research and drug discovery will also be addressed.
Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising ...preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell-cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.
Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically active compounds. Certain ...derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both chromone and pyrazole rings. The methods reviewed include the synthesis of chromone-pyrazole dyads, synthesis of chromone-pyrazole-fused compounds, and chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the chromone and pyrazole dual chemistry and their outcomes in the 21st century.
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•Polychaeteas were exposed to waterborne 100 nm polystyrene nanoplastics (PS NPs).•PS NPs exposure increase burrowing time and impair cholinesterase activity.•PS NPs can induce ...oxidative damage namely though increased protein oxidation.
Plastic debris has been reaching the world’s oceans since it started being used. Multiple studies have been addressing the effects of microplastics in various organisms but, despite the increased scientific awareness, there is still a significant gap in knowledge when it comes to small-sized plastic particles of sizes below 100 nm. The aim of this study was to understand the effect of waterborne 100 nm polystyrene nanoplastics (PS NPs) on the marine polychaeta Hediste diversicolor, a keystone species in intertidal and coastal environments, in terms of behavior, neurotransmission, oxidative status, energy metabolism and oxidative damage. Results of PS NPs characterization showed an aggregation along the time and with increasing concentrations. Results also revealed a considerable impact of PS NPs on ecologically relevant endpoints like cholinesterase (ChE) and burrowing, but no increases in most of the parameters associated with oxidative stress. Protein carbonylation was found to be more sensitive to PS NPs effects than lipid peroxidation. Behavioral alterations induced by PS NPs may affect nutrient cycling and (endo-)benthic fauna. The data revealed in this study highlighted the potential consequences of NPs to benthic organisms and the need for further studies.
Neglected parasitic diseases are a group of infections currently considered as a worldwide concern. This fact can be attributed to the migration of these diseases to developed and developing ...countries, associated with therapeutic insufficiency resulted from the low investment in the research and development of new drugs. In order to overcome this situation, bioprospecting supports medicinal chemistry in the identification of new scaffolds with therapeutically appropriate physicochemical and pharmacokinetic properties. Among them, we highlight the nitrogenous heterocyclic compounds, as they are secondary metabolites of many natural products with potential biological activity. The objective of this work was to review studies within a 10-year timeframe (2009- 2019), focusing on the pharmacological application of nitrogen bioprospectives (pyrrole, pyridine, indole, quinoline, acridine, and their respective derivatives) against neglected parasitic infections (malaria, leishmania, trypanosomiases, and schistosomiasis), and their application as a template for semi-synthesis or total synthesis of potential antiparasitic agents. In our studies, it was observed that among the selected articles, there was a higher focus on the attempt to identify and obtain novel antimalarial compounds, in a way that an extensive amount of studies involving all heterocyclic nitrogen nuclei were found. On the other hand, the parasites with the lowest number of publications up until the present date have been trypanosomiasis, especially those caused by Trypanosoma cruzi, and schistosomiasis, where some heterocyclics have not even been cited in recent years. Thus, we conclude that despite the great biodiversity on the planet, little attention has been given to certain neglected tropical diseases, especially those that reach countries with a high poverty rate.
The first COVID-19 case in Brazil was confirmed on February 25, 2020. On March 16, the state's governor declared public health emergency in the city of Rio de Janeiro and partial lockdown measures ...came into force a week later. The main goal of this work is to discuss the impact of the measures on the air quality of the city by comparing the particulate matter, carbon monoxide, nitrogen dioxide and ozone concentrations determined during the partial lockdown with values obtained in the same period of 2019 and also with the weeks prior to the virus outbreak. Concentrations varied with substantial differences among pollutants and also among the three studied monitoring stations. CO levels showed the most significant reductions (30.3–48.5%) since they were related to light-duty vehicular emissions. NO2 also showed reductions while PM10 levels were only reduced in the first lockdown week. In April, an increase in vehicular flux and movement of people was observed mainly as a consequence of the lack of consensus about the importance and need of social distancing and lockdown. Ozone concentrations increased probably due to the decrease in nitrogen oxides level. When comparing with the same period of 2019, NO2 and CO median values were 24.1–32.9 and 37.0–43.6% lower. Meteorological interferences, mainly the transport of pollutants from the industrial areas might have also impacted the results.
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•CO levels showed the most significant reductions during the partial lockdown.•NO2 decreased in a lower extent, due to industrial and diesel input.•PM10 levels were only reduced during the first partial lockout week.•Ozone increased due to the decrease in nitrogen oxides level in a VOC-controlled scenario.
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