Unveiling new myrsinoic acids and AChE ligands from Myrsine guianensis (Aubl.) Kuntze.

Molecular dereplication and drug-like discovery are important tools for exploring the chemical profile of metabolites in a complex mixture. In order to establish a workflow for discovering novel acetylcholinesterase (AChE) ligands, we performed the chemical study of Myrsine guianensis (Aubl.) Kuntze (Primulaceae). To carry out the bioprospection, nine extracts were obtained from different parts of the plant. Through the dereplication approaches, seventeen metabolites were annotated. In order to confirm the putative inferences, a HPLC preparative method was developed to isolate three known myrsinoic acids, A(1), B(2) and C(3). Along with, we are reporting the obtention of two new congeners, G(5) and H(6), which their structures were elucidated by NMR and HRMS data. Besides that, two extracts were submitted to affinity assays to accelerate the discovery of AChE ligands. Desorbates were analyzed through LC-HRMS for calculating the affinity ratio (AR). Thus, (1) presented AR = 4.59, therefore was considered a potential ligand.

Ligand fishing approach to explore Amaryllidaceae alkaloids as potential antiviral candidates targeting SARS-CoV-2 Nsp4.

Ligand fishing, also described as affinity-based assay, represents a convenient and efficient approach to separate potential ligands from complex matrixes or chemical libraries. This approach contributes to the identification of lead compounds that can bind to a specific target. In the context of COVID-19, the search for novel therapeutic agents is crucial. Small molecule-based antiviral drugs, such as Amaryllidaceae alkaloids, have been described as potential candidates because they can inhibit RNA viruses. Among various SARS-CoV-2 proteins, Nsp3, Nsp4, and Nsp6 play a crucial role in the pathogenicity of the virus and are attractive targets for developing COVID-19 treatments. These proteins are responsible for the replication/transcription complex (RTC) within double-membrane vesicles (DMVs), and their inhibition disrupts the virus's infectious cycle. Herein, we have successfully expressed and immobilized the SARS-CoV-2 Nsp4 protein on magnetic beads (Nsp4-MBs) and employed a ligand fishing assay to screen a collection of ten Amaryllidaceae-based alkaloids and applied to Hippeastrum aulicum extract. Remarkably, four out of ten alkaloids, namely 2-α-7-dimethoxyhomolycorine (6), haemanthamine (5), albomaculine (8), and tazettine (9), exhibited selective affinities for Nsp4. Albomaculine (8) and haemanthamine (5) were also identified from extract by the affinity assay. These findings highlight the potential of these alkaloids as model compounds for future drug discovery studies aimed at developing therapeutic interventions against SARS-CoV-2 infections.

A experiência fenomenológica e o trabalho em grupo na saúde mental / La experiencia fenomenológica y el trabajo en grupo en la salud mental / The experience phenomenological and the group work at mental health

Resumo O objetivo do estudo foi compreender o potencial terapêutico da experiência vivida em uma prática em grupo de promoção à saúde mental, que se singulariza por ter a finalidade de atenção à experiência cotidiana. O corpus estudado formou-se pela observação participante por dois anos e seis meses e por nove entrevistas abertas em profundidade com participantes do grupo, fundamentando-se no referencial teórico metodológico da Fenomenologia. A pesquisa analisou como os participantes compreendem a proposta de atenção à experiência e disposição do coordenador no processo grupal, bem como a valorização da condição existencial em detrimento da doença. Essa sistematização pôde favorecer com um eixo terapêutico em saúde mental diferente das intervenções hermenêuticas e educativas clássicas, colaborando com alternativas de cuidado em saúde e comunidade via atenção à experiência.

Resumen El objetivo del estudio fue comprender el potencial terapéutico de la experiencia vivida en una práctica en grupo de promoción de la salud mental que se singulariza por tener la finalidad de atención a la experiencia cotidiana. El corpus estudiado se formó por la observación participante por dos años y seis meses y por nueve entrevistas abiertas en profundidad con participantes del grupo, fundamentándose en el referencial teórico metodológico de la Fenomenología. La investigación analizó cómo comprenden los participantes la propuesta de atención a la experiencia y disposición del coordinador en el proceso grupal, así como la valorización de la condición existencial en detrimento de la enfermedad. Esa sistematización se puede favorecer con un eje terapéutico en salud mental diferente de las intervenciones hermenéuticas y educativas clásicas, colaborando con alternativas de cuidado en salud y comunidad.

Abstract The objective of this research was to understand the therapeutic potential of Experience in a group of mental health that distinguishes for having the purpose of attention to everyday experience. The study corpus was formed by the participant observation for two years and six months and nine open interviews with the participants of the group, based on methodological theoretical framework of Phenomenology. Among its findings, the participants describe the proposal of attention to experience and the coordinator position, as well highlighting the existential condition rather than the disease. This study could collaborate with a therapeutic axis in mental health not centered in hermeneutic or education intervention and could favor with the understanding of care alternatives through attention in mental and community health.

Acetylcholinesterase immobilized capillary reactors coupled to protein coated magnetic beads: a new tool for plant extract ligand screening.

The use of immobilized capillary enzyme reactors (ICERs) and enzymes coated to magnetic beads ((NT or CT)-MB) for ligand screening has been adopted as a new technique of high throughput screening (HTS). In this work the selected target was the enzyme acetylcholinesterase (AChE), which acts on the central nervous system and is a validated target for the treatment of Alzheimer's disease, as well as for new insecticides. A new approach for the screening of plant extracts was developed based on the ligand fishing experiments and zonal chromatography. For that, the magnetic beads were used for the ligand fishing experiments and capillary bioreactors for the activity assays. The latter was employed also under non-linear conditions to determine the affinity constants of known ligands, for the first time, as well as for the active fished ligand.

Agentes Comunitários de Saúde e os sentidos de "ser agente" / Community Health Agents and the meanings of

O Programa Saúde da Família constitui-se enquanto estratégia de mudança do modelo assistencial. O artigo apresenta os resultados de uma pesquisa qualitativa sobre os sentidos de 'ser agente' produzidos, por meio de entrevistas abertas, com Agentes Comunitários de Saúde que trabalham nos cinco Núcleos de Saúde da Família da cidade de Ribeirão Preto - São Paulo, vinculados à Faculdade de Medicina de Ribeirão Preto - USP. As entrevistas foram gravadas e transcritas na íntegra e analisadas segundo princípios da análise de conteúdo. A análise permitiu a descrição de sentidos acerca de ser agente subdivididos em: Sentidos produzidos na relação com a comunidade e Sentidos produzidos na relação com a equipe. A análise dos sentidos de ser agente possibilitou construir um diálogo sobre as tensões relacionadas a um fazer em saúde ora permeado por concepções atreladas ao modelo biomédico, ora atrelado aos novos paradigmas em saúde.(AU)

The Family Health Program consists of a strategy to change the health care model. This article presents the results from a qualitative study about the meanings of 'being an agent' obtained through open interviews with Community Health Agents who work in five Family Health Centers of the Ribeirão Preto School of Medicine (University of São Paulo), located in Ribeirão Preto, São Paulo. Interviews were tape recorded, fully transcribed, and then content analyzed. The analysis allowed for descriptions of meanings toward 'being an agent', subdivided into: Meanings produced by relationships with the community, and Meanings produced by relationships with the team. Analyzing the meanings of being an agent provided the establishment of a dialogue about the tensions related to a health practice that is at times influenced by conceptions associated with the biomedical method, and at other times with the new health paradigm.(AU)

Agentes Comunitários de Saúde e os sentidos de "ser agente" / Community Health Agents and the meanings of \"being an agent\"

O Programa Saúde da Família constitui-se enquanto estratégia de mudança do modelo assistencial. O artigo apresenta os resultados de uma pesquisa qualitativa sobre os sentidos de "ser agente" produzidos, por meio de entrevistas abertas, com Agentes Comunitários de Saúde que trabalham nos cinco Núcleos de Saúde da Família da cidade de Ribeirão Preto - São Paulo, vinculados à Faculdade de Medicina de Ribeirão Preto - USP. As entrevistas foram gravadas e transcritas na íntegra e analisadas segundo princípios da análise de conteúdo. A análise permitiu a descrição de sentidos acerca de ser agente subdivididos em: Sentidos produzidos na relação com a comunidade e Sentidos produzidos na relação com a equipe. A análise dos sentidos de ser agente possibilitou construir um diálogo sobre as tensões relacionadas a um fazer em saúde ora permeado por concepções atreladas ao modelo biomédico, ora atrelado aos novos paradigmas em saúde.

The Family Health Program consists of a strategy to change the health care model. This article presents the results from a qualitative study about the meanings of "being an agent" obtained through open interviews with Community Health Agents who work in five Family Health Centers of the Ribeirão Preto School of Medicine (University of São Paulo), located in Ribeirão Preto, São Paulo. Interviews were tape recorded, fully transcribed, and then content analyzed. The analysis allowed for descriptions of meanings toward "being an agent", subdivided into: Meanings produced by relationships with the community, and Meanings produced by relationships with the team. Analyzing the meanings of being an agent provided the establishment of a dialogue about the tensions related to a health practice that is at times influenced by conceptions associated with the biomedical method, and at other times with the new health paradigm.

The absolute configuration of 1-(3',4'-dihydroxycinnamoyl)cyclopentane-2,3-diol from the amazonian tree Chimarrhis turbinata.

An antioxidant, 1-(3',4'-dihydroxycinnamoyl)cyclopentane-2,3-diol [or (E)-2,3-dihydroxycyclopentyl-3-(3',4'-dihydroxyphenyl)acrylate (1)], and two known trans- and cis-chlorogenic acid methyl esters were isolated from the ethanolic extract of the leaves of Chimarrhis turbinata. The relative configuration of 1 was determined by NMR and by comparison of the circular dichroic spectrum (CD) with those of the enantiomers of synthetic 3',4'-dimethoxycinnamoyl analogues. The absolute configuration of one of the synthetic enantiomers was determined using the CD exciton chirality method. This established the structure of naturally occurring 1 as (E)-2,3-dihydroxycyclopentyl-3-(3',4'-dihydroxyphenyl)acrylate.

Turbinatine, a potential key intermediate in the biosynthesis of corynanthean-type indole alkaloids.

Extraction of the leaves of Chimarrhis turbinata has led to the isolation of turbinatine (1), a new corynanthean-type indole alkaloid, besides four known indole alkaloids, strictosidine, 5alpha-carboxystrictosidine, vallesiachotamine, and isovallesiachotamine. The structural determination of 1 was based on 1D and 2D spectroscopic data. An evaluation of the DNA-damaging activities of the isolates was performed by means of a bioassay using mutant strains of Saccharomyces cerevisiae, which indicated these compounds were weakly active.