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Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-kB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023) addressing their neuroprotective activity in vitro and in vivo.

Drimys winteri J.R. (Winteraceae) produce drimane sesquiterpenoids with activity against Candida yeast. In this work, drimenol, polygodial (1), isotadeonal (2), and a new drimane α,β-unsaturated 1,4-dialdehyde, named winterdial (4), were purified from barks of D. winteri. The oxidation of drimenol produced the monoaldehyde drimenal (3). These four aldehyde sesquiterpenoids were evaluated against six Candida species isolated from candidemia patients in Chilean hospitals. Results showed that 1 displays fungistatic activity against all yeasts (3.75 to 15.0 µg/mL), but irritant effects on eyes and skin, whereas its non-pungent epimer 2 has fungistatic and fungicide activities at 1.9 and 15.0 µg/mL, respectively. On the other hand, compounds 3 and 4 were less active. Molecular dynamics simulations suggested that compounds 1–4 are capable of binding to the catalytic pocket of lanosterol 14-alpha demethylase with similar binding free energies, thus suggesting a potential mechanism of action through the inhibition of ergosterol synthesis. According to our findings, compound 2 appears as a valuable molecular scaffold to pursue the future development of more potent drugs against candidiasis with fewer side effects than polygodial. These outcomes are significant to broaden the alternatives to treat fungal infections with increasing prevalence worldwide using natural compounds as a primary source for active compounds.

Fungal biotransformation is an attractive synthetic strategy to produce highly specific compounds with chemical functionality in regions of the carbon skeleton that are not easily activated by conventional organic chemistry methods. In this work

Memorias de atención primaria en salud es un libro colaborativo compuesto de ocho capítulos que tratan entre otros temas, acerca de educación para la salud, atención integral del niño, inmunización, y la alimentación.

Epothilone is a natural 16-membered macrolide cytotoxic compound produced by the metabolism of the cellulose-degrading myxobacterium Sorangium cellulosum. This review summarizes results in the study of epothilones against cancer with preclinical results and clinical studies from 2010–2022. Epothilone have mechanisms of action similar to paclitaxel by inducing tubulin polymerization and apoptosis with low susceptibility to tumor resistance mechanisms. It is active against refractory tumors, being superior to paclitaxel in many respects. Since the discovery of epothilones, several derivatives have been synthesized, and most of them have failed in Phases II and III in clinical trials; however, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that triple-negative breast cancer (TNBC) treatment improves using ixabepilone plus capecitabine or utidelone in combination with capecitabine. In recent years innovative synthetic strategies resulted in the synthesis of new epothilone derivatives with improved activity against refractory tumors with better activities when compared to ixabepilone or taxol. These compounds together with specific delivery mechanisms could be developed in anti-cancer drugs.

The alkaloids aristoteline (1), aristoquinoline (2), and aristone (3) were purified from the leaves of the Maqui tree Aristotelia chilensis and chemically characterized by NMR spectroscopy. The pharmacological activity of these natural compounds was evaluated on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) by Ca2+ influx measurements. The results suggest that these alkaloids do not have agonistic, but inhibitory, activity on each receptor subtype. The obtained IC50 values indicate the following receptor selectivity: hα3β4 > hα4β2 ≫ hα7. In the particular case of hα3β4 AChRs, 1 (0.40 ± 0.20 μM) and 2 (0.96 ± 0.38 μM) show higher potencies compared with 3 (167 ± 3 μM). Molecular docking and structure-activity relationship results indicate that ligand lipophilicity is important for the interaction with the luminal site located close to the cytoplasmic side of the hα3β4 ion channel between positions -2' and -4'. Compound 1 could be used as a molecular scaffold for the development of more potent noncompetitive inhibitors with higher selectivity for the hα3β4 AChR that could serve for novel addiction and depression therapies.

Extracts and compounds from the Chilean plants canelo, Drimys winteri J.R. Forst. & G. Forst. (Winteraceae), tabaco del diablo, Lobelia tupa L. (Campanulaceae), huevil, Vestia foetida Hoffmans. (Solanaceae) and violeta, Viola portalesia Gay (Violaceae) were evaluated against Sitophilus granarius L. (Coleoptera: Curculionidae), one of the most widespread and destructive primary pests of stored cereals. Total extracts at concentrations of 2.5%w/w in diets, over 6-days, display insecticidal effects against S. granarius. D. winteri caused the mortality of 87.5% of insects; L. tupa 80%, V. foetida 56% whereas V. portalesia killed 45% of insects under the same conditions. In an effort to determine the active compounds, the extracts of Lobelia tupa and Drimys winteri were purified by preparative chromatography. The piperidine alkaloid lobelanidine was isolated from L. tupa and the drimane sesquiterpenes drimenin, drimenol and polygodial were isolated as the major components in the extract from D. winteri. The purified compounds compounds displayed insecticidal activity against S. granarius in a concentration/dependent-time manner (% mortality at 0.5%w/w over 6-days): polygodial 80%, drimenol 60%, lobelanidine 47%, and drimenin 20%. In agreement with these results, grains treated with polygodial showed greater protection against the feeding attack by the granary weevil. These results provide evidence of the importance of elements of the native Chilean flora as new potential sources of botanical pesticides for the insect pest control.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but high-mortality drug hypersensitivity reaction, that requires early diagnosis and timely management. We present the case of a 32-year-old female patient with diagnosis of epilepsy and organic schizophreniform disorder, secondary to viral encephalitis, treated with multiple drugs, who presented diffuse habon-type skin rash, facial edema, fever, lymphadenopathy, leukocytosis with eosinophilia, and elevated transaminases, approximately 3 weeks after addition extended-release carbamazepine to her usual therapy. This drug was discontinue. Antihistamines and glucocorticoids were administered orally. Subsequently, the patient showed remarkable improvement.

It is reported in this study the effect of isolates from leaves of Aristotelia chilensis as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase enzymes. The aim of the paper was to evaluate the activity of A. chilensis towards different enzymes. In addition to pure compounds, extracts rich in alkaloids and phenolics were tested. The most active F5 inhibited AChE (79.5% and 89.8% at 10.0 and 20.0 μg/mL) and against BChE (89.5% and 97.8% at 10.0 and 20.0 μg/mL), showing a strong mixed-type inhibition against AChE and BChE. F3 (a mixture of flavonoids and phenolics acids), showed IC50 of 90.7 and 59.6 μg/mL of inhibitory activity against AChE and BChE, inhibiting the acetylcholinesterase competitively. Additionally, F3 showed and high potency as tyrosinase inhibitor with IC50 at 8.4 μg/mL. Sample F4 (anthocyanidins and phenolic composition) presented a complex, mixed-type inhibition of tyrosinase with a IC50 of 39.8 μg/mL. The findings in this investigation show that this natural resource has a strong potential for future research in the search of new phytotherapeutic treatments for cholinergic deterioration ailments avoiding the side effects of synthetic drugs. This is the first report as cholinesterases and tyrosinase inhibitors of alkaloids and phenolics from A. chilensis leaves.

The alkaloids aristoteline (

The vascular endothelium is a continuous monolayer of endothelial cells that are in direct contact with the blood and its dysfunction is the starting process in the development of many pathological inflammatory disorders, such as atherosclerosis, which can result in death. The expression of adhesion molecules such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) is a key stage in modulating vascular inflammation, where the adhesion of monocytes and their transmigration into the intima starting a cascade of inflammatory reactions. Looking for natural compounds with inhibitory activity of VCAM1 and ICAM1, we isolated drimenol, isodrimeninol and polygodial as the main secondary metabolites from barks of Drimys winteri (Dw) and evaluated their effects in the adhesion response of monocytes cells (THP1) to a monolayer of human umbilical vein endothelial cells (HUVEC) in coculture assays. The results showed that the molecules and total extract Dw decrease the adhesion of THP1 to HUVECs, at 10 μg/mL. The adhesion activity is explained due to the inhibition of VCAM1 and ICAM1 evidenced by qRT-PCR and Western-blot assays. In conclusion, drimane sesquiterpenoids could be used as a molecular scaffold in the development of drugs for inflammatory vascular diseases.

Early stages of atherosclerosis are characterizated for the uptake of oxidate low-density lipoprotein (oxLDL) by inflammatory macrophages in the arteries, promoting the foam cell formation. Drimys winteri is a native tree of Chile that produce drimane sesquiterpenoids, here it was evaluated the inhibitory foam cell formation by the total extract of barks of Drimys winteri and isodrimeninol, a sesquiterpenoid isolated from the tree. The results showed that Dw and isodrimeninol inhibited the foam cell formation on macrophage M1, by Oil Red O staining. Moreover, Dw reduced the gene expression of pro-inflammatory cytokine TNF-α, in contrast to isodrimeninol that showed not effect on the gene expression of this cytokine, also Dw enhanced the expression of the anti-inflammatory cytokine IL-10, in more significant manner than isodrimeninol at 20 μg/mL. While, Dw and isodrimeninol significantly reduced the expression of IL1-β at concentrations of 20 μg/mL, but not affecting the MMP-9 levels, assessed by RT-qPCR. In conclusion, Drimys winteri and isodrimeninol induce anti-atherosclerotic effects, inhibiting foam cell formation, as well as promoting anti-inflammatory responses. This study confirm the relevance of this tree as a medicinal source for the Mapuche people, and suggesting that Drimys winteri could be used in early stages of atherosclerosis.

Chagas disease is a neglected tropical disease that is caused by the protozoan Trypanosoma cruzi and represents a serious health problem, especially in Latin America. The clinical treatment of Chagas disease is based on two nitroderivatives that present severe side effects and important limitations. In folk medicine, natural products, including sesquiterpenoids, have been employed for the treatment of different parasitic diseases. In this study, the trypanocidal activity of compounds isolated from the Chilean plants Drimys winteri, Podanthus mitiqui and Maytenus boaria on three T. cruzi evolutive forms (epimastigote, trypomastigote and amastigote) was evaluated. Total extracts and seven isolated sesquiterpenoids were assayed on trypomastigotes and epimastigotes. Polygodial (Pgd) from D. winteri, total extract from P. mitiqui (PmTE) and the germacrane erioflorin (Efr) from P. mitiqui were the most bioactive substances. Pgd, Efr and PmTE also presented strong effects on intracellular amastigotes and low host toxicity. Many ultrastructural effects of these substances, including reservosome disruption, cytosolic vacuolization, autophagic phenotype and mitochondrial swelling (in the case of Pgd), were observed. Flow cytometric analysis demonstrated a reduction in mitochondrial membrane potential in treated epimastigotes and an increase in ROS production and high plasma membrane permeability after treatment with Pgd. The promising trypanocidal activity of these natural sesquiterpenoids may be a good starting point for the development of alternative treatmentsforChagas disease.

Objetivo: Determinar la frecuencia y tipos de hábitos higiénicos vulvo-vaginales en mujeres chilenas. Métodos: Estudio de corte transversal en 271 usuarias adultas que asistieron a centros ginecológicos primarios del sistema público y privado. Médico aplicó una encuesta de 7 preguntas con alternativas de respuestas cerradas para pesquisar la frecuencia y tipo de hábitos higiénicos íntimos. Se realizó estadística descriptiva utilizando modelos univariados y multivariados, expresando la magnitud de asociación como Odds Ratio. Se seleccionaron los modelos multivariados con mayor varianza mediante selección por pasos. Resultados: Un 25% lava sus genitales una vez/día, 32% dos veces/día, 28% tres veces/día y 13% cuatro o más veces/día. Las mujeres del sistema público tienden a un aseo genital con frecuencias de dos a tres veces al día, mientras que las del sistema privado mayormente una y dos veces al día. El 56% de las mujeres, especialmente aquellas atendidas en consultas privadas, utiliza algún otro elemento adicional al agua, preferentemente jabones especiales. Las mujeres mayores y postmenopáusicas se asociaron a lavados genitales con elementos adicionales al agua. Las diabéticas presentaron una probabilidad 3 veces mayor de usar un jabón especial que las no diabéticas. Conclusiones: Mujeres chilenas de ambos sistemas de atención, realizan aseo íntimo con una frecuencia entre una y tres veces al día en el 85% de las encuestadas. El 56% de ellas y el 75,6% de las que consultan en el sistema privado utilizan para el aseo genital algún otro elemento adicional al agua, preferentemente jabones especiales. Objective: To determine frequency and types of vulvovaginal hygienic habits that Chilean women have. Methods: Cross-sectional study in 271 adult women who attended primary gynecological centers of public and private systems. A survey of 7 questions with closed-answer alternatives was undertaken by a physician in order to determine frequency and type of intimate hygiene. Descriptive statistics were performed by using univariate and multivariate models, expressing the magnitude of association as Odds Ratio. Multivariate models with higher variance were selected by stepwise selection. Results: 25% washed their genitals once a day, 32% twice a day, 28% three times a day and 13% four or more times a day. Women attending public centers tend to wash their genitals two or three times a day, while the ones attending private centers do this mostly once or twice a day. 56% of women - especially those treated in private centers - use additional elements apart from water, preferably special soaps. Older and postmenopausal women were associated with the use of additional elements other than water. Diabetics were 3 times more likely to use a special soap than non-diabetics. Conclusions: 85% of chilean women of both health-care systems perform intimate hygiene between one and three times a day; 56% of them and 75.6% of those attending private centers use elements other than water, preferably special soaps.

The natural compound dendocarbin A, C15H22O3, is a sesquiterpene lactone isolated for the first time from Drimys winteri for var chilensis. The compound crystallizes in the orthorhombic space group P212121 and its X-ray crystal structure confirmed the S/R character of the chiral centres at C-5/C-10 and C-9/C-11, respectively. The α-OH group at C-11 was found to be involved in intermolecular hydrogen bonding, defining chains along the 21 screw axis. Fil: Paz Robles, Cristian. Universidad de La Frontera; Chile Fil: Burgos, Viviana. Universidad de La Frontera; Chile Fil: Suarez, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica; Argentina

The natural title compound, C11H12O4, extracted from the Chilean native tree Aristotelia chilensis (Maqui), is a polymorph of the synthetic E form reported by Xia, Hu & Rao [Acta Cryst. (2004), E60, o913-o914]. Both rotational conformers are identical from a metrical point of view, and only differ in the orientation of the 3,4-dihydroxyphenyl ring with respect to the rest of the molecule, which leads to completely different crystal structure arrangements and packing efficiencies. The reasons behind both reside in the different hydrogen-bonding interactions. Fil: Paz, Cristian. Universidad de Concepción; Chile Fil: Moreno, Yanko. Universidad de Concepción; Chile Fil: Becerra, José. Universidad de Concepción; Chile Fil: Silva, Mario. Universidad de Concepción; Chile Fil: Burgos, Viviana. Universidad de Concepción; Chile Fil: Freire Espeleta, Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Gerencia de Investigación Aplicada; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina Fil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica. Gerencia de Área de Aplicaciones de la Tecnología Nuclear. Gerencia de Investigación Aplicada; Argentina

The title compound, dendocarbin A [systematic name: (1R,5aS,9aS,9bR)-1-hydroxy-6,6,9a-trimethyldodecahydronaphtho[1,2-c]furan-3-one], C15H22O3, is a sesquiterpene lactone isolated from Drimys winteri var chilensis. The monoclinic phase described herein displays an identical molecular structure to the orthorhombic phase that we reported previously [Paz Robles et al. (2014). Acta Cryst. C70, 1007-1010], while varying significantly in chain pitch, and can thus be considered as a borderline case of one-dimensional isostructural polymorphism. Fil: Paz, Cristian. Universidad de La Frontera; Chile Fil: Burgos, Viviana. Universidad de La Frontera; Chile Fil: Suarez, Sebastian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica; Argentina

Este artículo presenta brevemente el resultado de un trabajo de investigación y de consulta bibliográfica, que consistió en la recopilación de modelos matemáticos para biorreactores y la solución numérica de algunos de ellos en la hoja de cálculo Microsoft Excel®. Se presenta, con fines principalmente didácticos, una alternativa para la exposición de dicha información en un módulo interactivo para computador. El módulo interactivo se creó con una nueva herramienta—HTML Help Workshop®— que permite una presentación de tipo educativo que puede ser publicada sin dificultad en Internet.

Lobelia tupa, also called devil's tobacco, is a native plant from the center-south of Chile which has been used by the native people of Chile as a hallucinogenic and anesthetic plant. A new piperidine alkaloid, called pentylsedinine, which comprises five carbons in the side chain, was isolated from the aerial part of L. tupa, along with lobeline and lobelanidine. The structure was established on the basis of 1D and 2D NMR spectroscopy. While lobeline is a neutral antagonist at alpha 3 beta 2/alpha 3 beta 4 nAChR and alpha 7 nAChR, both lobelanidine and pentylsedinine act as partial agonists at nAChR