Síntese de heterociclos bioativos derivados do ferroceno

The discovery of ferrocene marked one of the points of departure for modern organometallic chemistry. In general, the compounds of ferrocene derivatives are widely applied in several areas. One of the most important applications of ferrocene is the development of more active drugs, especially in cases where there is resistance to current drugs. Bioactive agents containing ferrocene have proven effective in combating diseases such as cancer, malaria, HIV, Alzheimer and conditions caused by fungi and bacteria. In this context, the present paper aims to highlights the synthesis of heterocycles containing ferrocene moiety and their use in medicinal chemistry.

Classificação multivariada de ervas medicinais da Região Amazônica e suas infusões de acordo com sua composição mineral

In this study, the mineral composition of leaves and teas of medicinal plants was evaluated. Ca, Cu, Fe, Mg, Mn e Zn were determined in the samples using flame atomic absorption spectrometry. Principal component analysis was applied to discriminate the samples studied. The samples were divided within the 2 groups according to their mineral composition. Copper and iron were the variables that contributed most to the separation of the samples followed by Ca, Mg, Mn and Zn. The information in the principal component analysis was confirmed by the dendrogram obtained by hierarchical cluster analysis.

Estudo das relações entre estrutura e atividade de parabenos: uma aula prática

Parabens are p-hydroxybenzoic acid esters widely used as preservatives. With the aim of teaching the structure-activity relationships (SAR) knowledge in a practical form, this paper proposed a practical class to view the SAR of parabens as antimicrobial agents. Methyl, ethyl, n-propyl, isopropyl and isopentyl paraben compounds were synthesized and their respective antimicrobial activities were assessed through determination of minimum inhibitory concentrations (MIC) against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 stains. With the MIC values, it was possible to verify theircorrelation with calculated lipophilicity (ClogP). This method can be applied in practical Medicinal Chemistry classes.

Doenças tropicais negligenciadas: uma nova era de desafios e oportunidades

In an article recently published in Química Nova, entitled "Chemistry Without Borders" ("Química Sem Fronteiras") [Pinto, A. C.; Zucco, C.; Galembeck, F.; Andrade, J. B.; Vieira, P. C. Quim. Nova 2012, 35, 2092], the authors highlighted the important aspects of science and technology with special emphasis on the field of Chemistry and its contributions toward a more prosperous Brazil of future. As a second step in that direction, this article extends the discussion of a key issue for the country in the framework of the chemistry community through the so called position papers in strategic areas. This document is a part of the contribution of the Brazilian Chemical Society to the World Science Forum to be held in Rio de Janeiro in November 2013. In this context, the present paper provides a brief discussion on neglected tropical diseases (NTDs) with emphasis on the current challenges and opportunities towards the development and evolution of the field. NTDs leads to illness, long-term disability or death, and has severe social, economic and psychological consequences for millions of men, women, and children worldwide. In most cases, the available treatments are inadequate and extremely limited in terms of efficacy and safety, leading to an urgent demand for new drugs. In addition to the traditional challenges involved in any drug discovery process, it is widely recognized that there is an innovation gap and a lack of investment for research and development (R&D) in the area of NTDs. In the last few decades, methods toward combating, eradication, prevention, and treatment of NTDs have been repeatedly emphasized in the major international agendas. Developments in these strategies and alliances have continued to have an essential impact, particularly in the area of drug discovery, both in Brazil and globally and should be encouraged and supported. Several examples of international activities dedicated to the reduction of the devastating global impact of NTDs can be provided. Despite the beneficial developments in the past 30 years, NTDs continue to devastate poor communities in remote and vulnerable areas, in large part, due to market failures and public policies. Recent studies have shown that among 756 new drugs approved between 2000 and 2011, only four new chemical entities (NCEs) were identified for the treatment of malaria, while none were developed against NTDs or tuberculosis. Furthermore, only 1.4% of approximately 150,000 clinical trials were registered for neglected diseases, with a smaller number of trials for NCEs. Establishment and strengthening of global strategies involving the triad "government-academia-industry" is fundamental to the success in R&D of new drugs for NTDs. National and international public-private initiatives that aim to create, encourage, and invest in R&D projects have been implemented and therefore are of utmost importance to successfully integrate Brazil into this new paradigm. It is essential to lay the foundation for mechanisms that will intensify investments in infrastructure, training, and qualification of personnel with an ultimate strategic vision that foresees continuity. Our research group has made significant contributions to the development of this field with the goal of forging new frontiers while tackling both current and future challenges that include indispensable elements such as innovation and integration.

Nanotecnologia em medicina: aspectos fundamentais e principais preocupações

The recent advances in the development of nanomaterials have opened new and exciting opportunities for their applications in medicine. These applications include molecular imaging, drug-delivery, and photothermal therapy. Despite the progress in medicinal applications of nanomaterials, several key problems remain unaddressed. Recent advances in this area include the enhancement of sensitivity in early diagnosis and therapy, in addition to investigations into the possible toxicity of nanomaterials. However, since little is known about the toxicity of nanomaterials, the regulation of these materials is a slow and complex process. This paper reviews the current scenario in the applications of nanomaterials in medicine as well as the main concerns and regulatory questions.

Chemical constituents isolated from turnera subulata Sm. and electrochemical characterization of phaeophytin b

Turnera subulata Sm., known as "Chanana" or "flor-do-Guarujá" in Brazilian folklore, is a plant species belonging to the subfamily Turneroideae of family Passifloraceae, which is used for various medicinal purposes in Brazil. The phytochemical study conducted here led to the isolation and identification of ten compounds present in T. subulata: two mixtures of steroids, sitosterol and stigmasterol (nonglycosylated and glycosylated); a mixture of flavonoids, 5,7,4′-trihidroxiflavona-8-C-α-glucopyranoside and 5,7,3′,4′-tetrahidroxiflavona-8-C-α-glucopyranosidel; and four phaeophytins, phaeophytin purpurin-18-phytyl ester, a rare natural product, phaeophytin a , 13²-hydroxy-(13²-S)-phaeophytin a , and phaeophytin b Phaeophytin b exhibited electrochemical activity similar to that of phthalocyanines.

Caracterização físico-química do óleo essencial da Siparuna guianensis Aublet

Thermal and spectroscopic analyses of essential oil extracted from Siparuna guianensis Aublet, an aromatic plant belonging to medicinal ethnobotany family Siparunaceae, were carried out. The plant is known throughout the North and Northeast of Brazil by the name negramina and has wide application as a natural insect repellent. Thermogravimetric analyses were correlated with the Arrhenius Equation to provide kinetic parameters of evaporation, including activation energy and frequency factor. Differential scanning calorimetric analysis showed the presence of an exothermic oxidation peak, probably as a result of transformations and decomposition of the solid structure before melting.

INTERAÇÕES FÁRMACO-RECEPTOR: APLICAÇÕES DE TÉCNICAS COMPUTACIONAIS EM AULA PRÁTICA SOBRE A EVOLUÇÃO DOS INIBIDORES DA ENZIMA CONVERSORA DE ANGIOTENSINA

Teaching classes and events regarding the molecular aspects of drug-receptor interactions is not an easy task. The ligand stereochemistry and the spatial arrangement of the macromolecular targets highly increase the complexity of the process. In this context, the use of alternative and more playful approaches could allow students to gain a more thorough understanding of this important topic in medicinal chemistry. Herein, we describe a practical teaching approach that uses computational strategies as a tool for drug-receptor interaction studies performed for angiotencsin converting enzyme inhibitors (ACEi). Firstly, the students learn how to find the crystallographic structure (enzyme-ligand complex). Then, they proceed to the treatment of crude crystallographic data. Thereafter, they learn how to analyze the positioning of the drug on the active site of the enzyme, looking for regions related to the molecular recognition. At the end of the study, students can summarize the molecular requirements for the interaction and the structure-activity relationships of the studied drugs.

Queima foliar e tombamento de mudas em plantas medicinais causadas por Rhizoctonia solani AG1 - 1B

Recentemente, em plantas medicinais da família Labiatae (Rosmarinus officinalis, Lavandula sp., Salvia officinalis e Thymus vulgaris), constatou-se tombamento de mudas em pós-emergência e queima foliar ascendente. Em isolamentos efetuados a partir de tecidos doentes, observou-se o desenvolvimento de um fungo com hifas ramificadas em ângulo de aproximadamente 90º, constrição na base da ramificação, septo próximo à inserção da hifa lateral e outras características típicas do gênero Rhizoctonia. Inoculou-se o fungo em plantas sadias cultivadas em vasos plásticos. Naquelas inoculadas por pincelamento de inóculo, ocorreu queima foliar de forma generalizada aos quatro dias da inoculação, enquanto nas inoculadas pela deposição de inóculo na superfície dos vasos, houve queima foliar ascendente, como observado em condições naturais, aos dez dias da inoculação. Com base na morfologia da colônia, crescimento micelial, número de núcleos, identificação do grupo e subgrupo de anastomose e da fase teleomórfica, o patógeno foi caracterizado como Rhizoctonia solani (fase anamórfica de Thanatephorus cucumeris). Com a reprodução dos sintomas da doença por inoculação artificial nas mudas e o reisolamento, em meio de batata dextrose ágar (BDA), do mesmo fungo a partir de tecidos doentes confirmou-se R. solani como o agente etiológico da doença.

Controle de Alternaria solani em tomateiro por extratos de Curcuma longa e curcumina: I. avaliação in vitro

A descoberta de compostos secundários de plantas medicinais com atividade antimicrobiana mostra-se promissora para o controle de fitopatógenos. A cúrcuma, Curcuma longa, apresenta em seus rizomas compostos com atividade antifúngica. Assim, o objetivo deste trabalho foi avaliar a fungitoxidade in vitro dos extratos de cúrcuma e da curcumina contra Alternaria solani. Foram utilizados extratos brutos aquosos (EB) de rizomas de cúrcuma (esterilizados por autoclavagem) nas concentrações de 0, 1, 5, 10 e 20% e curcumina nas concentrações de 0, 50, 100, 200 e 400 mg/L, os quais foram incorporados em meio de cultura batata-dextrose-ágar para avaliação de crescimento micelial e esporulação do fungo. Também foram testados extratos de cúrcuma a 10 e 15% esterilizados por filtração. O efeito dos extratos de cúrcuma autoclavados e não autoclavados e da curcumina na germinação de esporos in vitro foi também avaliado. Os extratos de cúrcuma a 10 e 15% não autoclavados inibiram em 38,2% e 23,2%, respectivamente, o crescimento micelial e 71,7% e 87%, respectivamente, a esporulação do fungo. Quando autoclavados, não apresentaram inibição do crescimento micelial nem da germinação de esporos e a inibição da esporulação foi menor, indicando a presença de compostos antimicrobianos termolábeis. O extrato não autoclavado na concentração de 5% inibiu em até 15% a germinação dos esporos. A curcumina inibiu o crescimento micelial em 29,5% na maior concentração testada, sem, contudo, afetar a esporulação e a germinação de esporos in vitro. Esses resultados indicam o potencial antifúngico da cúrcuma e curcumina contra A. solani.

Callus cell culture of Pothomorphe umbellata (L.) under stress condition leads to high content of peroxidase enzyme

Pothomorphe umbellata (L.) known on Brazil as Caapeba has a number of popular medicinal use, and it has been studied in relation to its pharmacological activity. Peroxidase specific activity (units/mg protein) was evaluated in callus cell culture samples of the P.umbellata, grown in two different MS medium (media 1 and media 2), submitted to 16 hours photoperiod or kept in darkness. Cell growth rate curve showed that the best growth indices were observed when media 2 submitted to the photoperiod regime was used, followed by the same media kept in darkness (stress condition). The results obtained also showed that the cell culture grown under stress conditions (darkness) lead to high content of peroxidase enzyme (an increase of 700% was observed). Kinetic constant values of 3.3 mmol.L-1 and 2,8 sec-1 were obtained for kM and v max,, respectively, using guaiacol as enzyme substrate.

Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by ¹H and 13C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), monoene anacardic acid (3), a-amirine (4), b-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp.

Dinâmica molecular: teoria e aplicações em planejamento de fármacos

Dinâmica Molecular (DM) é uma ferramenta computacional poderosa usada em Química Medicinal para o planejamento racional de fármacos. DM é uma extensão da Mecânica Molecular, onde o comportamento dinâmico de um sistema molecular é simulado através da integração numérica das equações de movimento. Esta técnica tem sido usada extensivamente para auxiliar e complementar o planejamento de novos ligantes de um alvo terapêutico, bem como estimar a sua potência. Este artigo enfoca a teoria básica da DM clássica e suas importantes aplicações no planejamento racional de potenciais compostos bioativos, particularmente compostos com atividade anti-HIV.

Validação de método analítico para análise de amitraz em mel utilizando GC/TSD

Este artigo descreve a validação de método analítico para determinação do acaricida amitraz em mel utilizando extração com n-hexano/acetona, cleanup em cartucho de extração em fase sólida (SPE) e análise por cromatografia a gás com detector termoiônico seletivo (GC-TSD). O método pode ser utilizado para monitorar a presença do pesticida amitraz em mel, devido aos bons parâmetros analíticos, precisão (CV<11%) e exatidão (>80%) dentro do intervalo 100-400 ng g-1. O limite estabelecido na União Européia, pelo Committee for Veterinary Medicinal Products, para amitraz em mel (200 ng g-1) está dentro deste intervalo. A resposta do sistema analítico apresentou linearidade entre 100 e 800 ng mL-1 com coeficiente de correlação de 0,9996, limite de detecção (LD-7 ng g-1) e de quantificação (LQ-100 ng g-1). O método validado foi utilizado para avaliar a qualidade de méis comercializados na cidade de Araraquara/SP, nas quais não foram detectados resíduos de amitraz.

Galhas e deformações em jambu (Spilanthes oleraceae)causadas por Tecaphora spilanthes (Ustilaginales)

A planta herbácea jambú, pertencente à família Asteracea, conhecida por diferentes nomes populares, como agrião do Pará, erva maluca, botão de ouro, etc., é uma espécie nativa da Amazônia, bastante utilizada na culinária regional e, também, apresenta importância medicinal e inseticida tendo sido, por este motivo, introduzida em Botucatu, SP. Nesta Nota é relatada a primeira constatação do carvão Tecaphora spilanthes Freire & Vànky no Estado de São Paulo. A infecção pode causar severas perdas e reduzir a qualidade das plantas.