Sulfur Compounds as Inhibitors of Enzymatic Activity of a Snake Venom Phospholipase A₂: Benzyl 4-nitrobenzenecarbodithioate as a Case of Study

Snakebite is a neglected disease with a high impact in tropical and subtropical countries. Therapy based on antivenom has limited efficacy in local tissue damage caused by venoms. Phospholipases A2 (PLA2) are enzymes that abundantly occur in snake venoms and induce several systemic and local effects. Furthermore, sulfur compounds such as thioesters have an inhibitory capacity against a snake venom PLA2. Hence, the objective of this work was to obtain a carbodithioate from a thioester with known activity against PLA2 and test its ability to inhibit the same enzyme. Benzyl 4-nitrobenzenecarbodithioate (I) was synthesized, purified, and characterized using as precursor 4-nitrothiobenzoic acid S-benzyl ester (II). Compound I showed inhibition of the enzymatic activity a PLA2 isolated from the venom of the Colombian rattlesnake Crotalus durissus cumanensis with an IC50 of 55.58 µM. This result is comparable with the reported inhibition obtained for II. Computational calculations were performed to support the study, and molecular docking results suggested that compounds I and II interact with the active site residues of the enzyme, impeding the normal catalysis cycle and attachment of the substrate to the active site of the PLA2.Facultad de Ciencias Exacta

Implementación de una secuencia didáctica a través de fábulas, mitos y leyendas para fortalecer la compresión lectora mediada por Google Classroom en los estudiantes del grado séptimo de la Institución Educativa Santa Elena de Medellín.

Este proyecto tiene como objeto fortalecer la comprensión lectora de estudiantes de séptimo grado en la I. E. Santa Elena de Medellín a través de una secuencia didáctica que empleó fábulas, mitos y leyendas en Google Classroom. El problema abordó la deficiencia en la comprensión lectora de estudiantes con dificultades en la interpretación de textos narrativos, reconocimiento de géneros literarios, la inferencia y crítica a partir de las lecturas ofrecidas. Los objetivos de esta investigación abarcaron un diagnóstico de la comprensión lectora, el diseño e implementación de la secuencia didáctica usando recursos educativos digitales y la evaluación de resultados después de su implementación. Los resultados de la investigación mostraron que la implementación de una secuencia didáctica utilizando fábulas, mitos y leyendas a través de Google Classroom contribuyó a fortalecer la comprensión lectora de los estudiantes.MaestríaMagíster en Recursos Digitales Aplicados a la Educació

Knowledge about Snake Venoms and Toxins from Colombia: A Systematic Review

Colombia encompasses three mountain ranges that divide the country into five natural regions: Andes, Pacific, Caribbean, Amazon, and Orinoquia. These regions offer an impressive range of climates, altitudes, and landscapes, which lead to a high snake biodiversity. Of the almost 300 snake species reported in Colombia, nearly 50 are categorized as venomous. This high diversity of species contrasts with the small number of studies to characterize their venom compositions and natural history in the different ecoregions. This work reviews the available information about the venom composition, isolated toxins, and potential applications of snake species found in Colombia. Data compilation was conducted according to the PRISMA guidelines, and the systematic literature search was carried out in Pubmed/MEDLINE. Venom proteomes from nine Viperidae and three Elapidae species have been described using quantitative analytical strategies. In addition, venoms of three Colubridae species have been studied. Bioactivities reported for some of the venoms or isolated components—such as antibacterial, cytotoxicity on tumoral cell lines, and antiplasmodial properties—may be of interest to develop potential applications. Overall, this review indicates that, despite recent progress in the characterization of venoms from several Colombian snakes, it is necessary to perform further studies on the many species whose venoms remain essentially unexplored, especially those of the poorly known genus Micrurus

Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase: Molecular Simulations and Experiments

Small molecule inhibitors of snake venom metalloproteinases (SVMPs) could provide a means to rapidly halt the progression of local tissue damage following viperid snake envenomations. In this study, we examine the ability of candidate compounds based on a pentacyclic triterpene skeleton to inhibit SVMPs. We leverage molecular dynamics simulations to estimate the free energies of the candidate compounds for binding to BaP1, a P-I type SVMP, and compare these results with experimental assays of proteolytic activity inhibition in a homologous enzyme (Batx-I). Both simulation and experiment suggest that betulinic acid is the most active candidate, with the simulations predicting a standard binding free energy of Δ G ∘ = − 11.0 ± 1.4 kcal/mol. The simulations also reveal the atomic interactions that underlie binding between the triterpenic acids and BaP1, most notably the electrostatic interaction between carboxylate groups of the compounds and the zinc cofactor of BaP1. Together, our simulations and experiments suggest that occlusion of the S1 ′ subsite is essential for inhibition of proteolytic activity. While all active compounds make hydrophobic contacts in the S1 ′ site, β -boswellic acid, with its distinct carboxylate position, does not occlude the S1 ′ site in simulation and exhibits negligible activity in experiment

Desquamative interstitial pneumonia : a change of diagnosis through multidisciplinary interstitial lung disease team evaluation

Q1Q1A1N

Biochemical and Functional Characterization of Anthocyanidin Reductase (ANR) from <i>Mangifera indica</i> L.

Mango (Mangifera indica L.) is abundant in proanthocyanidins (PAs) that are important for human health and plant response to abiotic stresses. However, the molecular mechanisms involved in PA biosynthesis still need to be elucidated. Anthocyanidin reductase (ANR) catalyzes a key step in PA biosynthesis. In this study, three ANR cDNAs (MiANR1-1,1-2,1-3) were isolated from mango, and expressed in Escherichia coli. In vitro enzyme assay showed MiANR proteins convert cyanidin to their corresponding flavan-3-ols, such as (&#8722;)-catechin and (&#8722;)-epicatechin. Despite high amino acid similarity, the recombinant ANR proteins exhibited differences in enzyme kinetics and cosubstrate preference. MiANR1-2 and MiANR1-3 have the same optimum pH of 4.0 in citrate buffer, while the optimum pH for MiANR1-1 is pH 3.0 in phosphate buffer. MiANR1-1 does not use either NADPH or NADH as co-substrate while MiANR1-2/1-3 use only NADPH as co-substrate. MiANR1-2 has the highest Km and Vmax for cyanidin, followed by MiANR1-3 and MiANR1-1. The overexpression of MiANRs in ban mutant reconstructed the biosynthetic pathway of PAs in the seed coat. These data demonstrate MiANRs can form the ANR pathway, leading to the formation of two types of isomeric flavan-3-ols and PAs in mango

Acute fibrinous and organizing pneumonia : a case report

Q1Q1Revista Internacional - IndexadaN

Standard Quality Characteristics and Efficacy of a New Third-Generation Antivenom Developed in Colombia Covering <i>Micrurus</i> spp. Venoms

In Colombia, Micrurus snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these types of antivenoms are scarce in certain areas of the country and are currently reported as an unavailable vital medicine. To address this issue, La Universidad de Antioquia, through its spin-off Tech Life Saving, is leading a project to develop third-generation polyvalent freeze-dried antivenom. The goal is to ensure access to this therapy, especially in rural and dispersed areas. This project aims to evaluate the physicochemical and preclinical parameters (standard quality characteristics) of a lab-scale anti-elapid antivenom batch. The antivenom is challenged against the venoms of several Micrurus species, including M. mipartitus, M. dumerilii, M. ancoralis, M. dissoleucus, M. lemniscatus, M. medemi, M. spixii, M. surinamensis, and M. isozonus, following the standard quality characteristics set by the World Health Organization (WHO). The antivenom demonstrates an appearance consistent with standards, 100% solubility within 4 min and 25 s, an extractable volume of 10.39 mL, a pH of 6.04, an albumin concentration of 0.377 mg/mL (equivalent to 1.22% of total protein), and a protein concentration of 30.97 mg/mL. Importantly, it maintains full integrity of its F(ab′)2 fragments and exhibits purity over 98.5%. Furthermore, in mice toxicity evaluations, doses up to 15 mg/mouse show no toxic effects. The antivenom also demonstrates a significant recognition pattern against Micrurus venoms rich in phospholipase A2 (PLA2) content, as observed in M. dumerilii, M. dissoleucus, and M. isozonus. The effective dose 50 (ED50) indicates that a single vial (10 mL) can neutralize 2.33 mg of M. mipartitus venom and 3.99 mg of M. dumerilii venom. This new anti-elapid third-generation polyvalent and freeze-dried antivenom meets the physicochemical parameters set by the WHO and the regulators in Colombia. It demonstrates significant efficacy in neutralizing the venom of the most epidemiologically important Micrurus species in Colombia. Additionally, it recognizes seven other species of Micrurus venom with a higher affinity for venoms exhibiting PLA2 toxins. Fulfilling these parameters represents the first step toward proposing a new pharmacological alternative for treating snakebites in Colombia, particularly in dispersed rural areas, given that this antivenom is formulated as a freeze-dried product

Snake venomics, experimental toxic activities and clinical characteristics of human envenomation by Bothrocophias myersi (Serpentes: Viperidae) from Colombia

Venoms of the viperid genus Bothrocophias, restricted to Colombia and Ecuador, are poorly known. Only a proteomic analysis of B. campbelli venom has been described. In this work we present a proteomic study of B. myersi venom, its biological activities, and describe the clinical characteristics of a patient bitten by this species. B. myersi venom mainly consists of phospholipases A2 (54.0%) and metalloproteinases (21.5%), among proteins of twelve different families. This venom exhibited proteolytic, phospholipase A2, myotoxic, edema-forming, and lethal activities. Enzymatic activities did not show statistically significant differences in comparison to Bothrops asper venom, but B. myersi venom displayed weaker hemorrhagic and coagulant activities. Polyvalent Viperidae antivenoms produced in Costa Rica and Colombia cross-recognized B. myersi venom by ELISA, however only the latter neutralized its lethal activity in mice when tested at a ratio of 3 mg venom/mL antivenom, suggesting it should be useful to treat envenomings inflicted by this species. A patient bitten by B. myersi developed edema and myotoxicity, evidenced by an increased creatine kinase activity in plasma. A good correlation was found between experimental biological activities of Bothrocophias myersi venom and the clinical features of an envenoming provoked by this species.Universidad de Antioquia/[]/UdeA/ColombiaUniversidad de Costa Rica/[]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP