Selênio, um elemento essencial à vida humana

Introdução: O Selênio ao mesmo tempo em que é tóxico se ingerido em grandes quantidades, é, também, micronutriente essencial em diversos processos metabólicos de animais e humanos. A deficiência de selênio vem sendo relacionada à predisposição em desenvolver doenças como o câncer, a diabetes, doenças cardiovasculares, entre outras. Na química medicinal, o selênio vem ganhando importância a partir da descoberta do ebselen, do ethaselen e do disseleneto de difenila. Objetivo: Essa revisão tem como objetivo compilar as principais informações disponíveis na literatura sobre a importância do selênio para a vida humana, proporcionando ao leitor uma visão geral do papel biológico desse elemento, das principais doenças relacionadas à deficiência de selênio, e da química medicinal dos três principais compostos de organoselênio. Metodologia: Foram recuperados artigos e teses acadêmicas que contemplassem o papel do selênio na bioquímica e na química medicinal, publicados em português e inglês, utilizando-se as bases de dados SciFinder, PubMed e Google Acadêmico. Resultados: Até o momento, foram identificadas 25 selenoproteínas que desempenham funções biológicas essenciais em animais e humanos. Sabe-se que a deficiência de selênio está diretamente relacionada à predisposição no desenvolvimento de diversas doenças. No campo da química medicinal, foi provado que é possível desenvolver moléculas bioativas, com baixa toxidez, contendo átomos de selênio em sua estrutura. Conclusão: O selênio é um elemento essencial à vida, sendo o componente-chave das selenoproteínas. O entendimento dos processos bioquímicos modulados por elas é imperativo para que os químicos medicinais possam desenvolver fármacos potentes contendo átomos de selênio em sua estrutura.

SUMMARY Introduction: Selenium is, at the same time, toxic if ingested in great amounts and an essential micronutrient to several metabolic processes in both animals and humans. Selenium deficiency is being related to an increased chance to develop diseases such as cancer, diabetes, cardiovascular diseases, among others. In medicinal chemistry, selenium has gained in importance since the discovery of ebselen, ethaselen, and diphenyl disselenide. Objectives: This review aims to compile the main data avail-able on the literature on the importance of selenium to human life, providing an overview of its biological role, the main diseases related to its deficiency, as well as the medicinal chemistry of the three most prominent organoselenium compounds. Methodology: Articles and academic thesis, published in English and Portuguese, showing the role of selenium in biochemistry and medicinal chemistry were recov-ered from SciFinder, PubMed, and Google Scholar. Results: So far, 25 selenopro-teins that play a biological role in humans and animals were identified. It is known that selenium deficiency is directly related not only to a predisposition to developing some diseases but is also the main cause of illnesses such as Keshan and Kashin-Beck. In the medicinal chemistry field, the development of selenium-containing bioactive compounds with low toxicity was proved possible. Conclusion: Selenium is an essential element to life, being the core component of selenoproteins. The under-standing of the biochemical processes modulated by those proteins is mandatory to medicinal chemists willing to develop potent organoselenium drugs.

Introducción: El selenioa la par que tóxico si se ingiere en grandes cantidades, es también un micronutriente esencial en varios procesos metabólicos en animales y humanos. La deficiencia de selenio se ha relacionado con una predisposición a desarrollar enfermedades como cáncer, diabetes, enfermedades cardiovasculares, entre otras. Em química médica, el selenio ha ganado importancia desde el descubrimiento del ebselen, etaselen y difenil diselenide. Objetivo: Esta revisión tiene como objetivo recopilar los principales datos disponibles en la literatura sobre la importancia del selenio para la vida humana, y proporcionar al lector una descripción general del papel biológico de este elemento, las principales enfermedades relacionadas con la deficiencia de este elemento, así como los compuestos de organoselenio más destacados. Metodología: Se recuperaron artículos y tesis académicas que contemplaban el papel del selenio en la bioquímica y la química médica, publicados en portugués e inglés, utilizando las bases de datos SciFinder, PubMed y Google Scholar. Resultados: Hasta el momento, se han identificado 25 selenoproteínas que realizan funciones biológicas esenciales en animales y humanos. Se sabe que la deficiencia de selenio está directamente relacionada con la predisposición en el desarrollo de varias dolencias, y también es la principal causa de enfermedades como las de Keshan y Kashin-Beck. En el campo de la química médica se ha comprobado que es posible desarrollar moléculas bioactivas, de baja toxicidad, que contengan átomos de selenio en su estructura. Conclusión: El selenio es un elemento esencial en la vida, siendo un componente central de las selenoproteínas. Comprender los procesos bioquímicos modulados por ellos es imperativo para que los químicos médicos puedan desarrollar fármacos potentes que contengan átomos de selenio en su estructura.

Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures.

BACKGROUND: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. METHODS: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. RESULTS: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic ß-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (ß- CD); fish bone powder; nanoparticle-based catalyst, among others. CONCLUSION: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei.

A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

Synthesis and biological evaluation of novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases as potential anticancer agents.

With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The nitro group of 2 was reduced to give the amino intermediate 3. Schiff bases 4a-r were obtained from coupling reactions between 3 and various benzaldehydes and heteroaromatic aldehydes. All the new compounds were fully identified and characterized by NMR (1H and 13C) and specifically for 4q by X-ray crystallography. The in vitro cytotoxicity of the compounds was evaluated against cancer cell lines (ACP-03, SKMEL-19 and HCT-116) by using MTT assay. Schiff bases 4b and 4o exhibited promising cytotoxicity against ACP-03 and SKMEL-19, respectively, with IC50 values lower than 5 µM. This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against cancer.

Oral effectiveness of PMIC4, a novel hydroxyethylpiperazine analogue, in Leishmania amazonensis.

Pentavalent antimonials have saved the lives of thousands of Leishmania-infected patients more than seventy years but, unfortunately, they are highly toxic and require parenteral delivery. Therefore, the search for safer and orally delivered alternative is a need. This paper describes the antileishmanial properties of PMIC4, a novel hydroxyethylpiperazine analogue. PMIC4 showed potent activity against intracellular amastigotes of Leishmania amazonensis, with IC50 of 1.8 µM and selectivity index higher than 100-fold, calculated in relation to the toxicity on the host cell. Following laboratory animal welfare policies, we analyzed the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and calculated the Lipinski's rule of five of PMIC4 before proceeding to in vivo tests. PMIC4 satisfied Lipinski's rule of five and presented high probability of human intestinal absorption, suggesting a good chance of druglikeness and oral bioavailability. For in vivo studies, PMIC4 was administered via intralesional injection (3.4 mg/kg/day, three times a week) or orally (34.0 mg/kg/day, five times a week) to L. amazonensis-infected BALB/c mice throughout the 98 day experiments. At the end of the treatment period, serum markers of toxicity were measured. When administered orally, PMIC4 controlled the lesions in L. amazonensis-infected BALB/c mice without altering serological markers of toxicity. These results demonstrate that PMIC4 is a promising molecular scaffold, orally effective against experimental leishmaniasis.