Assessing the Interactions between Snake Venom Metalloproteinases and Hydroxamate Inhibitors Using Kinetic and ITC Assays, Molecular Dynamics Simulations and MM/PBSA-Based Scoring Functions.

species are the main cause of snake bites in rural communities of tropical developing countries of Central and South America. Envenomation by snakes is characterized by prominent local inflammation, hemorrhage and necrosis as well as systemic hemostatic disturbances. These pathological effects are mainly caused by the major toxins of the viperidae venoms, the snake venom metalloproteinases (SVMPs).

Effects of strength training with free weights and elastic resistance in older adults: A randomised clinical study.

Background: The aging process leads to negative changes in various bodily systems, including the neuromuscular system. Strength training, is considered the best strategy to counteract these neuromuscular changes, preventing sarcopenia and frailty in older adults.

Objective: To compare the effects of strength training with elastic resistance and free weights on the muscle strength of knee extensors and flexors and functional performance in the older adults.

Zileuton, a 5-Lypoxigenase Inhibitor, is Antiparasitic and Prevents Inflammation in the Chronic Stage of Heart Chagas Disease.

Chronic Chagas cardiomyopathy is associated with an unbalanced immune response and impaired heart function, and available drugs do not prevent its development. Zileuton (Zi), a 5-lypoxigenase inhibitor, affects inflammatory/pro-resolution mediators. Herein, Zi treatment in the early phase of infection reduced parasitemia associated mainly with the direct effect of Zi on the parasite, and the enzyme epoxide hydrolase was the potential molecular target behind the trypanocidal effect.

Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.

Cruzipain (CZP), the major cysteine protease present in , the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti- activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages.

Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum.

In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L.

New drug discovery strategies for the treatment of benznidazole-resistance in , the causative agent of Chagas disease.

Introduction: Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD.

Areas Covered: Here, the authors review the current understanding of the molecular basis of benznidazole resistance.

New 2-nitroimidazole-N-acylhydrazones, analogs of benznidazole, as anti-Trypanosoma cruzi agents.

Chagas disease is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Worldwide, an estimated 8 million people are infected with T. cruzi, causing more than 10,000 deaths per year.

What are the barriers and facilitators to participation of people with Down syndrome? A scoping review.

Aim: To determine the barriers and facilitators of active community participation of children, adolescents, and adults with Down syndrome.

Method: Searches were completed in five electronic databases to identify original studies about participation of children, adolescents (ages < 18 years), and adults (ages 18-59 years) with Down syndrome. Barriers and facilitators to participation were categorized into four factors: personal, social, environmental, and policy and programme.

Aminopyrimidine Derivatives as Multiflavivirus Antiviral Compounds Identified from a Consensus Virtual Screening Approach.

Around three billion people are at risk of infection by the dengue virus (DENV) and potentially other flaviviruses. Worldwide outbreaks of DENV, Zika virus (ZIKV), and yellow fever virus (YFV), the lack of antiviral drugs, and limitations on vaccine usage emphasize the need for novel antiviral research. Here, we propose a consensus virtual screening approach to discover potential protease inhibitors (NS3) against different flavivirus.

Translation and validation of the audiovisual version of the Montreal cognitive assessment in older adults in Brazil.

Background: The use of a reliable remote cognitive screening test for older adults is crucial for the diagnosis of cognitive impairment. This study aimed to translate and validate the audiovisual Montreal Cognitive Assessment (MoCA)for older adults in Brazil.

Methods: One hundred and fourteen older adults were recruited from the community and demographic, functional, mood, and cognitive data were collected.

New anti-SARS-CoV-2 aminoadamantane compounds as antiviral candidates for the treatment of COVID-19.

Here, the antiviral activity of aminoadamantane derivatives were evaluated against SARS-CoV-2. The compounds exhibited low cytotoxicity to Vero, HEK293 and CALU-3 cells up to a concentration of 1,000 µM. The inhibitory concentration (IC) of aminoadamantane was 39.

Discovery and structural optimization of a new series of N-acyl-2-aminobenzothiazole as inhibitors of Zika virus.

Zika virus infection is associated to severe diseases such as congenital microcephaly and Zika fever causing serious harm to humans and special concern to health systems in low-income countries. Currently, there are no approved drugs against the virus, and the development of anti-Zika virus drugs is thus urgent. The present investigation describes the discovery and hit expansion of a N-acyl-2-aminobenzothiazole series of compounds against Zika virus replication.

Molecular targets for Chagas disease: validation, challenges and lead compounds for widely exploited targets.

Introduction: Chagas disease (CD) imposes social and economic burdens, yet the available treatments have limited efficacy in the disease's chronic phase and cause serious adverse effects. To address this challenge, target-based approaches are a possible strategy to develop new, safe, and active treatments for both phases of the disease.

Areas Covered: This review delves into target-based approaches applied to CD drug discovery, emphasizing the studies from the last five years.

Evaluating Known Zika Virus NS2B-NS3 Protease Inhibitor Scaffolds via In Silico Screening and Biochemical Assays.

The NS2B-NS3 protease (NS2B-NS3pro) is regarded as an interesting molecular target for drug design, discovery, and development because of its essential role in the Zika virus (ZIKV) cycle. Although no NS2B-NS3pro inhibitors have reached clinical trials, the employment of drug-like scaffolds can facilitate the screening process for new compounds. In this study, we performed a combination of ligand-based and structure-based in silico methods targeting two known non-peptide small-molecule scaffolds with micromolar inhibitory activity against ZIKV NS2B-NS3pro by a virtual screening (VS) of promising compounds.

Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors.

Discovery of novel SARS-CoV-2 main protease (M) inhibitors using a structure-based drug discovery strategy. Virtual screening employing covalent and noncovalent docking was performed to discover M inhibitors, which were subsequently evaluated in biochemical and cellular assays. 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 M with IC values of 0.

Multifunctional cotton fabrics with novel antibacterial coatings based on chitosan nanocapsules and polyacrylate.

Unlabelled: Chitosan is a cationic polysaccharide with intrinsic antimicrobial properties that can be used as an ecological alternative to develop functional materials to inhibit the proliferation of microorganisms. This work evaluates chitosan nanocapsules (CNs) as a self-disinfecting agent to provide bactericidal activity on cotton fabrics (CF), using polyacrylate to bind the CNs on the CF surface. The fabrics were characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle (CA), moisture retention, and antimicrobial tests against and .

Structure-based discovery of novel cruzain inhibitors with distinct trypanocidal activity profiles.

Over 110 years after the first formal description of Chagas disease, the trypanocidal drugs thus far available have limited efficacy and several side effects. This encourages the search for novel treatments that inhibit T. cruzi targets.

In vitro evaluation of antileishmanial activity, mode of action and cellular response induced by vanillin synthetic derivatives against Leishmania species able to cause cutaneous and visceral leishmaniasis.

The treatment against leishmaniasis presents problems, mainly due to their toxicity of the drugs, high cost and/or by the emergence of parasite resistant strains. In this context, new therapeutics should be searched. In this study, two novel synthetic derivatives from vanillin: [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] or 3s and [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde] or 3t, were evaluated regarding their antileishmanial activity against distinct parasite species able to cause cutaneous and visceral leishmaniasis.

Synthesis of vanillin derivatives with 1,2,3-triazole fragments and evaluation of their fungicide and fungistatic activities.

Vanillin is the main component of natural vanilla extract and is responsible for its flavoring properties. Besides its well-known applications as an additive in food and cosmetics, it has also been reported that vanillin can inhibit fungi of clinical interest, such as Candida spp., Cryptococcus spp.

It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (-quinone/-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929.

Screening the Pathogen Box to Discover and Characterize New Cruzain and CatL Inhibitors.

Chagas disease and Human African Trypanosomiasis, caused by and , respectively, pose relevant health challenges throughout the world, placing 65 to 70 million people at risk each. Given the limited efficacy and severe side effects associated with current chemotherapy, new drugs are urgently needed for both diseases. Here, we report the screening of the Pathogen Box collection against cruzain and CatL, validated targets for Chagas disease and Human African Trypanosomiasis, respectively.

Experimental and Computational Study of Aryl-thiosemicarbazones Inhibiting Cruzain Reveals Reversible Inhibition and a Stepwise Mechanism.

is a parasite that infects about 6-7 million people worldwide, mostly in Latin America, causing Chagas disease. Cruzain, the main cysteine protease of , is a validated target for developing drug candidates for Chagas disease. Thiosemicarbazones are one of the most relevant warheads used in covalent inhibitors targeting cruzain.