Treatment using vanillin-derived synthetic molecules incorporated into polymeric micelles is effective against infection caused by Leishmania amazonensis species.

Treatment against leishmaniasis presents problems, mainly due to the toxicity of the drugs, high cost, and the emergence of resistant strains. A previous study showed that two vanillin-derived synthetic molecules, 3s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], presented antileishmanial activity against Leishmania infantum, L. amazonensis, and L. braziliensis species. In the present work, 3s and 3t were evaluated to treat L. amazonensis-infected mice. Molecules were used pure or incorporated into Poloxamer 407-based micelles. In addition, amphotericin B (AmpB) and its liposomal formulation, Ambisome®, were used as control. Animals received the treatment and, one and 30 days after, they were euthanized to evaluate immunological, parasitological, and biochemical parameters. Results showed that the micellar compositions (3s/Mic and 3t/Mic) induced significant reductions in the lesion mean diameter and parasite load in the infected tissue and distinct organs, as well as a specific and significant antileishmanial Th1-type immune response, which was based on significantly higher levels of IFN-γ, IL-12, nitrite, and IgG2a isotype antibodies. Drug controls showed also antileishmanial action; although 3s/Mic and 3t/Mic have presented better and more significant parasitological and immunological data, which were based on significantly higher IFN-γ production and lower parasite burden in treated animals. In addition, significantly lower levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in mice treated with 3s/Mic and 3t/Mic, when compared to the others. In conclusion, results suggest that 3s/Mic and 3t/Mic could be considered as therapeutic candidates to treat against L. amazonensis infection.

New synthetic molecules incorporated into polymeric micelles used for treatment against visceral leishmaniasis.

Treatment against visceral leishmaniasis (VL) presents problems, mainly related to drug toxicity, high cost and/or by emergence of resistant strains. In the present study, two vanillin synthetic derivatives, 3 s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3 t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], were evaluated as therapeutic candidates in a murine model against Leishmania infantum infection. Molecules were used pure (3 s and 3 t) or incorporated into Poloxamer 407-based micelles (3 s/M and 3 t/M) in the infected animals, which also received amphotericin B (AmpB) or Ambisome® as control. Results showed that 3 s/M and 3 t/M compositions induced a Th1-type immune response in treated animals, with higher levels of IFN-γ, IL-2, TNF-α, IL-12, nitrite, and IgG2a antibodies. Animals presented also low toxicity and significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as compared as control groups mice, with the evaluations performed one and 30 days after the application of the therapeutics. In conclusion, preliminary data suggest that 3 s/M and 3 t/M could be considered for future studies as therapeutic agents against VL.

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

Aim: Discovery of novel SARS-CoV-2 main protease (Mpro) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover Mpro inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 Mpro with IC50 values of 0.4-3 µM. They were also shown to inhibit SARS-CoV-1 Mpro and human cathepsin L. Molecular dynamics simulations indicated the stability of the Mpro inhibitor complexes and the interaction of ligands at the subsites. Conclusion: This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 Mpro inhibitors.

Boltzmann's equation at 150: Traditional and modern solution techniques for charged particles in neutral gases.

Seminal gas discharge experiments of the late 19th and early 20th centuries laid the foundations of modern physics, and the influence of this "golden era" continues to resonate well into the 21st century through modern technologies, medical applications, and fundamental scientific investigations. Key to this continuing success story has been the kinetic equation formulated by Ludwig Boltzmann in 1872, which provides the theoretical foundations necessary for analyzing such highly non-equilibrium situations. However, as discussed here, the full potential of Boltzmann's equation has been realized only in the past 50 years or so, with modern computing power and analytical techniques facilitating accurate solutions for various types of charged particles (ions, electrons, positrons, and muons) in gases. Our example of thermalization of electrons in xenon gas highlights the need for such accurate methods-the traditional Lorentz approximation is shown to be hopelessly inadequate. We then discuss the emerging role of Boltzmann's equation in determining cross sections by inverting measured swarm experiment transport coefficient data using machine learning with artificial neural networks.

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. Results showed that compounds 3s and 3t were effective against Leishmania infantum, L. amazonensis and L. braziliensis promastigote and amastigote-like forms, showing selectivity index (SI) of 25.1, 18.2 and 22.9, respectively, when 3s was used against promastigotes, and of 45.2, 7.5 and 15.0, respectively, against amastigote-like stage. Using the compound 3t, SI values were 45.2, 53.0 and 80.0, respectively, against promastigotes, and of 35.9, 46.0 and 58.4, respectively, against amastigote-like forms. Amphotericin B (AmpB) showed SI values of 5.0, 7.5 and 15.0, respectively, against promastigotes, and of 3.8, 5.0 and 7.5, respectively, against amastigote-like stage. The treatment of infected macrophages and inhibition of the infection upon pre-incubation with the molecules showed that they were effective in reducing the infection degree and inhibiting the infection in pre-incubated parasites, respectively, as compared to data obtained using AmpB. The mechanism of action of 3s and 3t was evaluated in L. infantum, revealing that both 3s and 3t altered the parasite mitochondrial membrane potential leading to reactive oxygen species production, increase in lipid corps and changes in the cell cycle, causing the parasite' death. A preliminary assay using the cell culture supernatant from treated and infected macrophages showed that 3s and 3t induced higher IL-12 and lower IL-10 values; suggesting the development of an in vitro Th1-type response in the treated cells. In this context, data indicated that 3s and 3t could be considered therapeutic agents to be tested in future studies against 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., Aspergillus spp., as well as dermatophytes. Thus, the present work approaches the synthesis of a series of vanillin derivatives with 1,2,3-triazole fragments and the evaluation of their antifungal activities against Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans, Cryptococcus gattii, Trichophyton rubrum, and Trichophyton interdigitale strains. Twenty-two vanillin derivatives were obtained, with yields in the range of 60%-91%, from copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction between two terminal alkynes prepared from vanillin and different benzyl azides. In general, the evaluated compounds showed moderate activity against the microorganisms tested, with minimum inhibitory concentration (MIC) values ranging from 32 to >512 µg mL-1 . Except for compound 3b against the C. gattii R265 strain, all vanillin derivatives showed fungicidal activity for the yeasts tested. The predicted physicochemical and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties for the compounds indicated favorable profiles for drug development. In addition, a four-dimensional structure-activity relationship (4D-SAR) analysis was carried out and provided useful insights concerning the structures of the compounds and their biological profile. Finally, molecular docking calculations showed that all compounds bind favorably at the lanosterol 14α-demethylase enzyme active site with binding energies ranging from -9.1 to -12.2 kcal/mol.

Anthelmintic effect of a water soluble Moringa oleifera lectin in rodents experimentally infected with Haemonchus contortus.

Allied to the problem of gastrointestinal parasites, especially Haemochus contortus, the use of lectins of plant origin has contributed to the research of alternative anthelmintics. The nematicidal effect of a water soluble Moringa oleifera lectin (WSMoL) was investigated in an experimental model with H. contortus infected Wistar rodents. Three concentrations were tested orally: 5 mg/kg, 2.5 mg/kg and 1 mg/kg. The reduction in the number of larvae recovered in the experimental groups was analyzed, as well as biochemical, hematological and histological parameters. Treatments with 5, 2.5 and 1 mg/kg of WSMoL reduced the number of larvae recovered of animals by 74.7 %, 72.8 % and 66 %, respectively. Untreated infected animals had anemia, moderate mononuclear multifocal hepatitis, vascular congestion in the liver and kidneys, white pulp hyperplasia in the spleen, and presence of eosinophils in the intestine. Infected animals treated with 5 mg/kg of WSMoL showed liver with moderate bleeding, kidney with vascular congestion, spleen with white pulp hyperplasia and intestine with moderate presence of mononuclear cells. An increase in the serum level of glutamic pyruvic transaminase and a reduction in the level of hemoglobin (p < 0.001) were also observed in this group when compared to the uninfected group. However, the administered concentrations of 2.5 and 1 mg/kg of WSMoL were both satisfactory in terms of reducing the number of recovered larvae and not promoting negative changes in the biochemical, hematological and histological parameters evaluated. These results indicate an in vivo nematicidal effect of WSMoL on the H. contortus parasite.

Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus.

Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions using new vectors, such as Aedes aegypti, and has the potential to cause serious epidemics in the future. Currently, there are no vaccines or specific treatments against MAYV. In this study, the antiviral activity of a series of synthetic cyclic ketones were evaluated for the first time against MAYV. Twenty-four compounds were screened in a cell viability assay, and eight were selected for further evaluation. Effective concentration (EC50) and selectivity index (SI) were calculated and compound 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) (EC50 = 21.5 µmol·L-1, SI = 15.8) was selected for mechanism of action assays. The substance was able to reduce viral activity by approximately 70% in both pre-treatment and post-treatment assays.

The Ring-LWE Problem in Lattice-Based Cryptography: The Case of Twisted Embeddings.

Several works have characterized weak instances of the Ring-LWE problem by exploring vulnerabilities arising from the use of algebraic structures. Although these weak instances are not addressed by worst-case hardness theorems, enabling other ring instantiations enlarges the scope of possible applications and favors the diversification of security assumptions. In this work, we extend the Ring-LWE problem in lattice-based cryptography to include algebraic lattices, realized through twisted embeddings. We define the class of problems Twisted Ring-LWE, which replaces the canonical embedding by an extended form. By doing so, we allow the Ring-LWE problem to be used over maximal real subfields of cyclotomic number fields. We prove that Twisted Ring-LWE is secure by providing a security reduction from Ring-LWE to Twisted Ring-LWE in both search and decision forms. It is also shown that the twist factor does not affect the asymptotic approximation factors in the worst-case to average-case reductions. Thus, Twisted Ring-LWE maintains the consolidated hardness guarantee of Ring-LWE and increases the existing scope of algebraic lattices that can be considered for cryptographic applications. Additionally, we expand on the results of Ducas and Durmus (Public-Key Cryptography, 2012) on spherical Gaussian distributions to the proposed class of lattices under certain restrictions. As a result, sampling from a spherical Gaussian distribution can be done directly in the respective number field while maintaining its format and standard deviation when seen in Zn via twisted embeddings.

Leishmanicidal and cytotoxic activities and 4D-QSAR of 2-arylidene indan-1,3-diones.

The indan-1,3-dione and its derivatives are important building blocks in organic synthesis and present important biological activities. Herein, the leishmanicidal and cytotoxicity evaluation of 16 2-arylidene indan-1,3-diones is described. The compounds were evaluated against the leukemia cell lines HL60 and Nalm6, and the most effective ones were 2-(4-nitrobenzylidene)-1H-indene-1,3(2H)-dione (4) and 4-[(1,3-dioxo-1H-inden-2(3H)-ylidene)methyl]benzonitrile (10), presenting IC50 values of around 30 µmol/L against Nalm6. The leishmanicidal activity was assessed on Leishmania amazonensis, with derivative 4 (IC50 = 16.6 µmol/L) being the most active. A four-dimensional quantitative structure-activity analysis (4D-QSAR) was applied to the indandione derivatives, through partial least-squares regression. The statistics presented by the regression models built with the selected field descriptors of Coulomb (C) and Lennard-Jones (L) nature, considering the activities against L. amazonensis, HL60, and Nalm6 leukemia cells, were, respectively, R2 = 0.88, 0.92, and 0.98; Q2 = 0.83, 0.88, and 0.97. The presence of positive Coulomb descriptors near the carbonyl groups indicates that these polar groups are related to the activities. Besides, the presence of positive Lennard-Jones descriptors close to substituents R3 or R1 indicates that bulky nonpolar substituents in these positions tend to increase the activities. This study provides useful insights into the mode of action of indandione derivatives for each biological activity involved.

Fostering Responsible Innovation in Health: An Evidence-Informed Assessment Tool for Innovation Stakeholders.

BACKGROUND: Responsible innovation in health (RIH) emphasizes the importance of developing technologies that are responsive to system-level challenges and support equitable and sustainable healthcare. To help decision-makers identify whether an innovation fulfills RIH requirements, we developed and validated an evidence-informed assessment tool comprised of 4 inclusion and exclusion criteria, 9 assessment attributes and a scoring system. METHODS: We conducted an inter-rater reliability assessment to establish the extent to which 2 raters agree when applying the RIH Tool to a diversified sample of health innovations (n=25). Following the Tool's 3-step process, sources of information were collected and cross-checked to ensure their clarity and relevance. Ratings were reported independently in a spreadsheet to generate the study's database. To measure inter-rater reliability, we used: a non-adjusted index (percent agreement), a chance-adjusted index (Gwet's AC) and the Pearson's correlation coefficient. Results of the Tool's application to the whole sample of innovations are summarized through descriptive statistics. RESULTS: Our findings show complete agreement for the screening criteria, "almost perfect" agreement for 7 assessment attributes, "substantial" agreement for 2 attributes and "almost perfect" agreement for the RIH overall score. A large portion of the sample obtained high scores for 6 attributes (health relevance, health inequalities, responsiveness, level and intensity of care and frugality) and low scores for 3 attributes (ethical, legal, and social issues [ELSIs], inclusiveness and eco-responsibility). At the rating step, 88% of the innovations had a sufficient number of attributes documented (≥ 7/9), but the assessment was based on sources of moderate to high quality (mean score ≥ 2 points) for 36% of the sample. While "Almost all RIH features" were present for 24% of the innovations (RIH mean score between 4.1-5.0 points), "Many RIH features" were present for 52% of the sample (3.1-4.0 points) and "Few RIH features" were present for 24% of the innovations (2.1-3.0 points). CONCLUSION: By confirming key aspects of the RIH Tool's reliability and applicability, our study brings its development to completion. It can be jointly put into action by innovation stakeholders who want to foster innovations with greater social, economic and environmental value.

Isobenzofuran-1(3H)-ones as new tyrosinase inhibitors: Biological activity and interaction studies by molecular docking and NMR.

Tyrosinase is a multifunctional, glycosylated and copper-containing oxidase enzyme that can be found in animals, plants, and fungi. It is involved in several biological processes such as melanin biosynthesis. In this work, a series of isobenzofuran-1(3H)-ones was evaluated as tyrosinase inhibitors. It was found that compounds phthalaldehydic acid (1), 3-(2,6-dihydroxy-4-isopropylphenyl)isobenzofuran-1(3H)-one (7), and 2-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-1,3-phenylene diacetate (9) were the most potent compounds inhibiting tyrosinase activity in a concentration dependent manner. Ligand-enzyme NMR studies and docking investigations allowed to map the atoms of the ligands involved in the interaction with the copper atoms present in the active site of the tyrosinase. This behaviour is similar to kojic acid, a well know tyrosinase inhibitor and used as positive control in the biological assays. The findings herein described pave the way for future rational design of new tyrosinase inhibitors.

In vitro effects of Moringa oleifera seed lectins on Haemonchus contortus in larval and adult stages.

Haemonchus contortus is a hematophagous parasite causing damage to the production of ruminant animals throughout the world. This study evaluated the in vitro effect of proteins from Moringa oleifera (WSMoL - Water Soluble M. oleifera Lectin and cMoL - coagulant M. oleifera Lectin) on the motility of infective larvae and adult male and female worms of H. contortus. The specific activity of total proteases and the morphology of the worms exposed to the lectins were observed. Both lectins inhibited motility of all parasite stages tested. WSMoL and cMoL at 500 µg mL-1 interfered in the motility of larvae. Values of 11.1% and 8.1% were the lowest motility indices of larvae with sheath, and 30.6% and 16.4% were the lowest motility indices of exsheathed larvae treated with WSMoL and cMoL, respectively. In 1 mg mL-1 solutions of WSMoL and of cMoL, the motility index of adult male worms was 23.3% (p < 0.001) and 20% (p < 0.001), while the motility index of adult female worms was 63.3% (p > 0.05) and 26.6% (p < 0.001), respectively. Greater proteolytic activity was detected in extracts obtained from adult worms, male and female, after incubation with the lectins. Morphological changes caused by the lectins were revealed by changes in the crests of the cuticle, in the longitudinal striations and at the vulva.

Microbial nanocellulose adherent to human skin used in electrochemical sensors to detect metal ions and biomarkers in sweat.

The pursuit of biocompatible, breathable and skin-conformable wearable sensors has predominantly focused on synthetic stretchable hydrophobic polymers. Microbial nanocellulose (MNC) is an exceptional skin-substitute natural polymer routinely used for wound dressing and offers unprecedented potential as substrate for wearable sensors. A versatile strategy for engineering wearable sensing platforms is reported, with sensing units made of screen-printed carbon electrodes (SPCEs) on MNC. As-prepared SPCEs were used to detect the toxic metals cadmium (Cd2+) and lead (Pb2+) with limits of detection of 1.01 and 0.43 µM, respectively, which are sufficient to detect these metal ions in human sweat and urine. SPCEs functionalized through anodic pre-treatments were used for detecting uric acid and 17ß-estradiol in artificial sweat, with detection limits of 1.8 µM and 0.58 µM, respectively. The electrochemical treatment created oxygen groups on the carbon surfaces, thus improving wettability and hydrophilicity. MNC was herein exploited as an adhesive-free, yet highly skin-adherent platform for wearable sensing devices that also benefit from the semi-permeable, non-allergenic, and renewable features that make MNC unique within the pool of materials that have been used for such a purpose. Our findings have clear implications for the developments on greener and more biocompatible but still efficient substrates and may pave the route for combining immunosensing devices with drug delivery therapies.

Crystal structure of histidine ammonia-lyase from Trypanosoma cruzi.

Chagas disease is one of seventeen neglected tropical diseases according to the World Health Organization (WHO). The histidine-glutamate metabolic pathway is an oxidative route that has shown to be relevant for the bioenergetics in Trypanosoma cruzi, the etiological agent for Chagas disease. Histidine ammonia-lyase participates in the first stage of the histidine catabolism, catalyzing the conversion of l-histidine into urocanate. This work presents the three-dimensional (3D) structure of Trypanosoma cruzi histidine ammonia-lyase enzyme (TcHAL) and some comparisons of it to homologous structures. The enzyme was expressed, purified and assayed for crystallization, what allowed the obtainment of crystals of sufficient quality to collect X-ray diffraction data up to 2.55 Å resolution. After refinement, some structural analyses indicated that the structure does not contain the active site protection domain, in opposition to previously known 3D structures from plants and fungi phenylalanine ammonia-lyase, therefore, it is the first structure of eukaryotic ammonia-lyases that lacks this domain.

Pesticides in the surface waters of the Camanducaia River watershed, Brazil.

Camanducaia River is part of the Piracicaba watershed responsible for pumping water into the Cantareira System, which is one of the main water sources for the metropolis of São Paulo and Campinas, Brazil. Intensive use of pesticides and hilly topography represents a situation of high risk for river water contamination. Therefore, water samples from 12 locations were collected along the Camanducaia River and its tributaries, over a period of 4 mo during the rainy season, and analyzed by GC-MS/MS or UPLC- MS/MS for the presence of 46 pesticides. Seven pesticides (fipronil, methyl parathion, metolachlor, atrazine, carbofuran, diuron, and simazine) were positively detected. Only atrazine (the most frequently detected) and diuron were present at concentrations above the limit of quantification of the analytical method (0.32 and 0.57 µg L-1 for atrazine and diuron, respectively). Pesticides detection frequency was higher than expected for a river system where only 11.8% of the land area is under agriculture. The vulnerability of the Camanducaia basin to pesticide contamination is attributed to the high annual precipitation (> 1.5 m y-1 in the headwaters), associated with topographical features (steep terrain) and soil types that favor surface runoff, which has been exacerbated by poor soil management practices.

Ecological Biosubstrates Obtained from Onion Pulp (Allium cepa L.) for Flexible Organic Light-Emitting Diodes.

A new biopolymer obtained from onion pulp (Allium cepa L.) was employed to produce a sustainable substrate for flexible organic light-emitting diodes (FOLEDs). Indium tin oxide (ITO) and SiO2 thin films were deposited by rf-magnetron sputtering onto these biosubstrates to obtain flexible, transparent, and conductive anodes, on top of which FOLEDs were produced. This new biomaterial exhibits an optical transparency of 63% at 550 nm. ITO films were optimized by varying rf power during deposition onto the biopolymers, and their electrical properties are comparable to the those of ITO grown on top of rigid substrates: a carrier concentration of -3.63 × 1021 cm-3 and carrier mobility of 7.72 cm2 V-1 s-1 for the optimized film. Consequently, the sheet resistance and resistivity of this ITO film were 8.92 Ω sq-1 and 2.23 × 10-4 Ω cm, respectively, hence allowing the production of FOLEDs. The A. cepa L. based FOLED was fabricated using CuPc, ß-NPB, and Alq3 as organic layers, and it exhibited a maximum luminance of about 2062 cd m-2 at 16.6 V. The current efficiency reached a maximum value of 2.1 cd A-1 at 85.3 mA cm-2. The obtained results suggest the possibility to use these substrates for innovative biocompatible applications in optoelectronics, such as photodynamic therapy.

Discovery of novel West Nile Virus protease inhibitor based on isobenzonafuranone and triazolic derivatives of eugenol and indan-1,3-dione scaffolds.

The West Nile Virus (WNV) NS2B-NS3 protease is an attractive target for the development of therapeutics against this arboviral pathogen. In the present investigation, the screening of a small library of fifty-eight synthetic compounds against the NS2-NB3 protease of WNV is described. The following groups of compounds were evaluated: 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones; eugenol derivatives bearing 1,2,3-triazolic functionalities; and indan-1,3-diones with 1,2,3-triazolic functionalities. The most promising of these was a eugenol derivative, namely 4-(3-(4-allyl-2-methoxyphenoxy)-propyl)-1-(2-bromobenzyl)-1H-1,2,3-triazole (35), which inhibited the protease with IC50 of 6.86 µmol L-1. Enzyme kinetic assays showed that this derivative of eugenol presents competitive inhibition behaviour. Molecular docking calculations predicted a recognition pattern involving the residues His51 and Ser135, which are members of the catalytic triad of the WNV NS2B-NS3 protease.

Therapeutic potential of low-cost nanocarriers produced by green synthesis: macrophage uptake of superparamagnetic iron oxide nanoparticles.

Aim: The primary goal of this work was to synthesize low-cost superparamagnetic iron oxide nanoparticles (SPIONs) with the aid of coconut water and evaluate the ability of macrophages to internalize them. Our motivation was to determine potential therapeutic applications in drug-delivery systems associated with magnetic hyperthermia. Materials & methods: We used the following characterization techniques: x-ray and electron diffractions, electron microscopy, spectrometry and magnetometry. Results: The synthesized SPIONs, roughly 4 nm in diameter, were internalized by macrophages, likely via endocytic/phagocytic pathways. They were randomly distributed throughout the cytoplasm and mainly located in membrane-bound compartments. Conclusion: Nanoparticles presented an elevated intrinsic loss power value and were not cytotoxic to mammalian cells. Thus, we suggest that low-cost SPIONs have great therapeutic potential.

New insights towards mesoporous silica nanoparticles as a technological platform for chemotherapeutic drugs delivery.

Mesoporous silica nanoparticles (MSNs) displays interesting properties for biomedical applications such as high chemical stability, large surface area and tunable pores diameters and volumes, allowing the incorporation of large amounts of drugs, protecting them from deactivation and degradation processes acting as an excellent nanoplatform for drug delivery. However, the functional MSNs do not present the ability to transport the therapeutics without any leakage until reach the targeted cells causing side effects. On the other hand, the hydroxyls groups available on MSNs surface allows the conjugation of specific molecules which can binds to the overexpressed Enhanced Growth Factor Receptor (EGFR) in many tumors, representing a potential strategy for the cancer treatment. Beyond that, the targeting molecules conjugate onto mesoporous surface increase its cell internalization and act as gatekeepers blocking the mesopores controlling the drug release. In this context, multifunctional MSNs emerge as stimuli-responsive controlled drug delivery systems (CDDS) to overcome drawbacks as low internalization, premature release before to reach the region of interest, several side effects and low effectiveness of the current treatments. This review presents an overview of MSNs fabrication methods and its properties that affects drug delivery as well as stimuli-responsive CDDS for cancer treatment.