Programa de pesquisa em produtos naturais: a experi��ncia da CEME

The Brazilian effort on R&D of products from the national biodiversity dates back to the 70's. The Central de Medicamentos - CEME - was tailored to add scientific and technological competence to the production of pharmaceutical drugs derived from the Brazilian biodiversity by means of the Research Programme on Medicinal Plants - PPPM. Although previous to the Convention on Biological Diversity - CBD - and to the current debate and the ever-growing interest on phytomedicines, CEME has historical importance in the present governmental efforts on fostering the R&D on phytomedicines. This article makes a historical redemption of the PPPM, the actions and the results in the course of its existence.

Produtos naturais como candidatos a f��rmacos ��teis no tratamento do Mal de Alzheimer

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD and natural products have played an important role in the research for new acetylcholinesterase inhibitors.

Produtos naturais da asc��dia Botrylloides giganteum, das esponjas Verongula gigantea, Ircinia felix, Cliona delitrix e do nudibr��nquio Tambja eliora, da costa do Brasil

Two new marine metabolites, 3Z, 6Z, 9Z-dodecatrien-1-ol (1) from the ascidian Botrylloides giganteum and 4H-pyran-2ol acetate from the sponge Ircinia felix (4) are herein reported. The known bromotyrosine compounds, 2-(3,5-dibromo-4-methoxyphenyl)-N,N,N-dimethylethanammonium (2) and 2,6-dibromo-4-(2-(trimethylammonium)ethyl)phenol (3), have been isolated from the sponge Verongula gigantea. Serotonin (5) is reported for the first time from the sponge Cliona delitrix, and tambjamines A (15) and D (16) isolated as their respective salts from the nudibranch Tambja eliora. Only tambjamine D presented cytotoxicity against CEM (IC50 12.2 µg/mL) and HL60 (IC50 13.2 µg/mL) human leukemya cells, MCF-7 breast cancer cells (IC50 13.2 µg/mL), colon HCT-8 cancer cells (IC50 10.1 µg/mL) and murine melanoma B16 cancer cells (IC50 6.7 µg/mL).

Os produtos naturais e a qu��mica medicinal moderna

Natural products have been utilized by humans since ancient times and the relief and cure of their diseases was the first purpose for using natural products in medicine. The history of the oriental and occidental civilizations is very rich in examples of the utilization of natural products in medicine and health care. Chinese traditional medicine is one of the most important examples of how natural products can be efficient in the treatment of diseases, and it points to the importance of scientific research on natural products, concerning the discovery of new active chemical entities. The complexity, chemical diversity and biological properties of natural products always fascinated people, and during the last 200 years, this led to the discovery of important new drugs. In the last 30 years, the development of new bioassay techniques, biotechnology methods, bio-guided phytochemical studies, automated high throughput screening and high performance analytical methods, have introduced new concepts and possibilities of rational drug design and drug discovery. In this context, natural products have played an important and decisive role in the development of modern medicinal chemistry.

Espectroscopia de Resson��ncia Magn��tica Nuclear de 13C no estudo de rotas biossint��ticas de produtos naturais

During the last five decades, as a result of an interaction between natural product chemistry, synthetic organic chemistry, molecular biology and spectroscopy, scientists reached an extraordinary level of comprehension about the natural processes by which living organisms build up complex molecules. In this context, 13C nuclear magnetic resonance spectroscopy, allied with isotopic labeling, played a determinant role. Nowadays, the widespread use of modern NMR techniques allows an even more detailed picture of the biochemical steps by accurate manipulation of the atomic nuclei. This article focuses on the development of such techniques and their impact on biosynthetic studies.

Isolamento e atividades biol��gicas de produtos naturais das esponjas monanchora arbuscula, aplysina sp. petromica ciocalyptoides e topsentia ophiraphidites, da asc��dia didemnum ligulum e do octocoral carijoa riisei

The investigation of extracts from six species of marine invertebrates yielded one new and several known natural products. Isoptilocaulin from the sponge Monanchora aff. arbuscula displayed antimicrobial activity at 1.3 mg/mL against an oxacillin-resistant strain of Staphylococcus aureus. Five inactive known dibromotyrosine derivatives, 2 6, were isolated from a new species of marine sponge, Aplysina sp. The sponges Petromica ciocalyptoides and Topsentia ophiraphidites yielded the known halistanol sulfate A (7) as an inhibitor of the antileishmanial target adenosine phosphoribosyl transferase. The ascidian Didemnum ligulum yielded asterubin (10) and the new N,N-dimethyl-O-methylethanolamine (11). The octocoral Carijoa riisei yielded the known 18-acetoxypregna-1,4,20-trien-3-one (12), which displayed cytotoxic activity against the cancer cell lines SF295, MDA-MB435, HCT8 and HL60.

Biologia qu��mica: uma estrat��gia moderna para a pesquisa em produtos naturais

This paper presents an overview of the Natural Products Research in Brazil in the last five years (2002-2006), and also discusses how some relevant aspects of the Chemical Biology area could create new research opportunities and challenges for the natural product chemists. In addition, some aspects of the scientific policies and their impact on current projects are discussed.

Fotoprotetores derivados de produtos naturais: perspectivas de mercado e intera����es entre o setor produtivo e centros de pesquisa

Ultraviolet radiation is the major exogenous mediators of skin damage. To prevent such damage, sunscreen products are used. New research aims at both the elucidation of new sunscreen compounds, as well as new assets for supporting and synergistic action. In this article it is presented a systematic data of innovation for sunscreen and a discussion on prospects for partnership between universities and enterprises, where it is believed that the innovations in cosmetics, driven by the constant demand of the market in new products, may be a stimulus for the interactions between university and company in Brazil.

Utiliza����o de detec����o por espalhamento de luz evaporativo para a an��lise de produtos naturais

The interest in the use of evaporative light scattering detector (ELSD) for the analysis of different classes of natural products has grown over the years. This is because this detector has become an excellent alternative compared to other types of detectors, such as the refractive index detector and the ultraviolet (UV) detector. This review describes the basic principles of ELSD functioning and discusses the advantages and disadvantages in using an ELSD for the analysis of organic compounds. Additionaly, an overview, covering the last 23 years, of ELSD applications in natural products analysis (saponins, terpenes, carbohydrates, glycosides, alkaloids, steroids, flavonoids, peptides, polyketides, coumarins and iridoids) is presented and discussed.

Explorando produtos naturais microbianos nas fronteiras da Qu��mica e da Biologia

The chemistry of natural products has been remarkably growing in the past few decades in Brazil. Aspects related to the isolation and identification of new natural products, as well as their biological activities, have been achieved in different laboratories working on this subject in the country. More recently, the introduction of new molecular biology tools has strongly influenced the research on natural products, mainly those produced by microorganisms, creating new possibilities to assess the chemical diversity of secondary metabolites. This paper describes some ideas on how the research on natural products can have a considerable input from molecular biology in the generation of chemical diversity. We also explore the role of microbial natural products in mediating interspecific interactions and their relevance to ecological studies. Examples of the generation of chemical diversity are highlighted by using genome mining, mutasynthesis, combinatorial biosynthesis, metagenomics, and synthetic biology, while some aspects of microbial ecology are also discussed. The idea to bring up this topic is linked to the remarkable development of molecular biology techniques to generate useful chemicals from different organisms. Here, we focus mainly on microorganisms, even though similar approaches have also been applied to the study of plants and other organisms. Investigations in the frontier of chemistry and biology require interactions between different areas, characterizing the interdisciplinarity of this research field. The necessity of a real integration of chemistry and biology is pivotal to finding correct answers to a number of biological phenomena. The use of molecular biology tools to generate chemical diversity and control biosynthetic pathways is largely explored in the production of important biologically active compounds. Finally, we briefly comment on the Brazilian organization of research in this area, the necessity of new strategies for the graduation programs, and the establishment of networks as a way of organization to overcome some of the problems faced in the area of natural products.

Eclos��o e mortalidade de Meloidogyne exigua em extratos e em produtos naturais

A eclos��o e mortalidade de juvenis de segundo est��dio (J2) de Meloidogyne exigua foram avaliadas em extratos aquosos de urucum-colorau (Bixa orellana), cravo-da-��ndia (Syzygium aromaticum), canela (Cinnamomum zeylanicum), pimenta-do-reino (Piper nigrum), gengibre (Zingiber officinale), salsa (Petroselium crispum), soro de leite, solu����o nutritiva hidrop��nica, solu����o aquosa de cloreto de s��dio (NaCl) e a����car (sacarose), fermento biol��gico e probi��tico (Controlmix��). O soro de leite e os extratos de canela, fermento biol��gico e cloreto de s��dio causaram 100% de mortalidade (P<0,05) ap��s 24 h do contato dos J2 com os extratos. Mortalidade acima de 50% tamb��m ocorreu nos extratos de cravo-da-��ndia e no probi��tico. Os demais materiais testados foram estatisticamente iguais �� ��gua (P<0,05). A eclos��o foi avaliada durante 16 dias de imers��o dos ovos de M. exigua nos extratos. Comparando os valores da ��rea abaixo da curva de progresso da eclos��o, observou-se que, exceto o a����car e a solu����o hidrop��nica, todos os extratos e produtos testados inibiram a eclos��o (P<0,01) dos J2 de M. exigua. Entre todos os extratos e produtos testados, maior inibi����o (P<0,01) da eclos��o ocorreu no soro de leite, probi��tico, canelaecravo-da-��ndia, destacando-se o soro de leite e o extrato de canela que assim como inibiram a eclos��o tamb��m foram altamente t��xicos aos juvenis.

Produtos naturais aplicados para manejo de Meloidogyne incognita em tomateiros

Este trabalho teve por objetivo avaliar o efeito de produtos naturais na express��o da resist��ncia a Meloidogyne incognita em plantas de tomate produzidos organicamente. Os indutores Rocksil, Quitosana, Neemseto e Biopirol foram aplicados 5, 10 e 15 dias, em tratamentos independentes, antes da inocula����o do pat��geno atrav��s da pulveriza����o foliar, utilizando-se duas dosagens para cada indutor. A inocula����o do nematoide foi realizada 30 dias ap��s o plantio, usando-se 5000 ovos/ planta. Avaliando-se o n��mero de ovos e o fator de reprodu����o, 30 dias ap��s a inocula����o, observou-se que todos os tratamentos diferiram estatisticamente da testemunha, impedindo o aumento da popula����o inicial do pat��geno. Dentre os indutores, o indutor silicatado Rocksil foi o que apresentou os melhores resultados para o controle da meloidoginose em todas as ��pocas de aplica����o e em todas as dosagens. Contudo, plantas tratadas com o produto apresentaram baixos pesos de parte a��rea sugerindo que houve um custo adaptativo de resist��ncia. Considerando-se o fator de reprodu����o n��o foram observadas diferen��as estat��sticas quando comparadas a dosagem e ��poca de aplica����o entre os indutores, com exce����o da Quitosana aplicada aos 5 dias antes da inocula����o e do Neemseto aplicado aos 15 dias antes da inocula����o do nemat��ide.

Efici��ncia de produtos naturais no controle de Colletotrichum gloeosporioides em pimenta na p��s colheita

O objetivo do trabalho foi avaliar o efeito de produtos naturais na express��o da resist��ncia a Colletotrichum gloeosporioides agente etiol��gico da antracnose, em frutos p��s-colheita de pimenta. Os produtos acadian��, biopirol��, neemseto��, quitosana e rocksil�� foram aplicados em duas ��pocas, 48 e 72 horas antes da inocula����o do pat��geno, em tratamentos independentes, utilizando-se duas dosagens para cada indutor. Verificou-se uma diminui����o no desenvolvimento do pat��geno em todos os tratamentos, diferindo estatisticamente da testemunha. Na primeira ��poca de aplica����o (48h) os tratamentos com biopirol�� seguidos do acadian�� nas maiores dosagens, apresentaram menores les��es de antracnose em rela����o aos demais tratamentos desta ��poca. Na segunda ��poca de aplica����o (72h) o produto acadian�� foi o ��nico que apresentou efeito significativo entre os demais tratamentos. Os resultados obtidos demonstram potencial dos indutores naturais no controle da antracnose em frutos de pimenta na p��s-colheita.

ESTUDO DO PROCESSO DA EXTRA����OSUPERCR��TICA DE ��LEOS ESSENCIAIS DE PRODUTOS NATURAIS

A desterpena����o do ��leo essencial de laranja �� uma preocupa����o da ind��stria c��trica. Esta consiste em concentrar os componentes oxigenados do ��leo, que s��o os maiores respons��veis pelo sabor e aroma deste, reduzindo a fra����o terp��nica que se degrada facilmente promovendo a forma����o de compostos com sabores e aroma indesej��veis. Esta fra����o oleosa rica em compostos oxigenados pode ser empregada em bebidas e outros alimentos como aromatizante mais agrad��vel. Um dos m��todos em estudo para a concentra����o dos compostos oxigenados do ��leo essencial de laranja �� a adsor����o na s��lica gel, seguida da dessor����o fracionada com di��xido de carbono pressurizado. Este processo permite a obten����o de fra����es oleosas mais concentradas em compostos oxigenados que outros m��todos convencionais. Neste trabalho foi utilizado o modelo de difus��o em s��lido aplicado em leito fixo, empregando a solu����o anal��tica proposta por Rosen em 1952, para o estudo do modelamento do processo de dessor����o do ��leo essencial de laranja com di��xido de carbono supercr��tico.

Avalia����o de produtos naturais no controle de biofilmes formados em sistema din��mico

The biofilms microbial forms of association are responsible for generating, accelerating and / or induce the process of corrosion. The damage generated in the petroleum industry for this type of corrosion is significatives, representing major investment for your control. The aim of this study was to evaluate such tests antibiograms the effects of extracts of Jatropha curcas and essential oil of Lippia gracilis Schauer on microrganisms isolated from water samples and, thereafter, select the most effective natural product for further evaluation of biofilms formed in dynamic system. Extracts of J. curcas were not efficient on the complete inhibition of microbial growth in tests type antibiogram, and essential oil of L. gracilis Schauer most effective and determined for the other tests. A standard concentration of essential oil of 20 &#956;L was chosen and established for the evaluation of the biofilms and the rate of corrosion. The biocide effect was determined by microbial counts of five types of microorganisms: aerobic bacteria, precipitating iron, total anaerobic, sulphate reducers (BRS) and fungi. The rate of corrosion was measured by loss of mass. Molecular identification and scanning electron microscopy (SEM) were performed. The data showed reduction to zero of the most probable number (MPN) of bacteria precipitating iron and BRS from 115 and 113 minutes of contact, respectively. There was also inhibited in fungi, reducing to zero the rate of colony-forming units (CFU) from 74 minutes of exposure. However, for aerobic and anaerobic bacteria there was no significant difference in the time of exposure to the essential oil, remaining constant. The rate of corrosion was also influenced by the presence of oil. The essential oil of L. gracilis was shown to be potentially effective