The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

Oxisol subsurface chemical attributes related to sugarcane productivity

Embora haja homogeneidade nas características morfológicas na classe dos Latossolos, existe grande diversidade química na subsuperfície. Trabalhos indicam que a produção agrícola apresenta correlação significativa com atributos químicos de subsuperfície, que são mais estáveis que na camada arável, sujeita a alterações decorrentes da exploração agrícola. Pelo exposto, o presente estudo avaliou os efeitos dos atributos químicos de subsuperfície de Latossolos da região Centro-Sul do Brasil na produtividade agrícola dos três primeiros cortes de clones de cana-de-açúcar e da variedade RB72454. Utilizaram-se os dados de produtividade agrícola correspondentes ao período de 1993 a 1998. Os solos foram caracterizados sob o ponto de vista granulométrico e químico na profundidade entre 0,8 e 1,0 m e foram feitos estudos de correlação entre tais atributos e as médias de produtividade agrícola diária durante o ciclo dos clones de cada ensaio e da variedade RB72454 e análise de regressão múltipla, com as variáveis selecionadas pelo procedimento stepwise em função do R². As características químicas de subsuperfície dos Latossolos influenciaram na produtividade agrícola da cana-de-açúcar, principalmente no 3º corte. Para as médias dos clones, o modelo de produtividade do 3º corte em função de saturação por bases e fósforo, mostra R² = 0,31, ou seja, que 31% da variação de TCH dia-1 pode ser explicada por esses dois atributos. No caso da variedade RB72454, essa mesma variação no 3º corte é explicada em 47% pelos atributos soma de bases e teores de cálcio e matéria orgânica. As variações de produtividade de 1º e 2º cortes foram melhor explicadas pelo pHágua.

Tropical biodiversity: has it been a potential source of secondary metabolites useful for medicinal chemistry?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

OS produtos naturais e a química 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.

Propagação e desenvolvimento inicial defícus adhatodifolia Schott ex Spreng. (Moraceae) em diferentes temperaturas, intensidades luminosas e substratos

Pós-graduação em Agronomia (Horticultura) - FCA

Estudo químico de Jatropha curcas e de Jatropha gossypifolia nativas e cultivadas: avaliação de ciclopeptídeos em função de habitat e hábito : prospecção e atividade biológica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento de método analítico para estudo metabolômico de cana-de-açucar

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo químico e biológico do fungo endofítico C80 (Phaeosphaeriaceae) associado à alga marinha Bostrychia radicans

Pós-graduação em Química - IQ

Obtenção de derivados semissintéticos dos alcalóides (-) - cassina e (-) e espectalina e avaliação do potencial antimalárico

Pós-graduação em Química - IQ

Estudo químico e biológico de fungos endofíticos isolados das folhas de Styrax camporum Pohl (Styracaceace)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Variabilidade genética e química entre e dentro de populações de Casearia sylvestris Sw. (Salicaceae) no estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Diversidade morfológica, genética e química de populações naturais de Anemopaegma arvense (Vell.) Stellf

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo da biologia reprodutiva, diversidade genética e química de populações de Ocimum selloi Benth

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Busca de substâncias bioativas em fungos associados com a espécie Michelia champaca L. (Magnoliaceae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Metabolômica, uma abordagem otimizada para exploração da biodiversidade brasileira: estado da arte, perspectivas e desafios

Brazilian biodiversity is a colossal source of secondary metabolites with remarkable structural features, which are valuable in further biodiscovery studies. In order to fully understand the relations and interactions of a living system with its surroundings, efforts in natural product chemistry are directed toward the challenge of detecting and identifying all the molecular components present in complex samples. It is plausible that this endeavor was born out of recent technological sophistication in secondary metabolite identification with sensitive spectroscopic instruments (MS and NMR) and higher resolving power of chromatographic systems, which allow a decrease in the amount of required sample and time to acquire data. Nevertheless, the escalation of data acquired in these analyses must be sorted with statistical and multi-way tools in order to select key information. Chromatography is also of paramount importance, more so when selected compounds need to be isolated for further investigation. However, in the course of pursuing a greener environment, new policies, with an aim to decrease the use of energy and solvents, are being developed and incorporated into analytical methods. Metabolomics could be an effective tool to answer questions on how living organisms in our huge biodiversity work and interact with their surroundings while also being strategic to the development of high value bio-derived products, such as phytotherapeutics and nutraceuticals. The incorporation of proper phytotherapeutics in the so-called Brazilian Unified Health System is considered an important factor for the urgent improvement and expansion of the Brazilian national health system. Furthermore, this approach could have a positive impact on the international interest toward scientific research developed in Brazil as well as the development of high value bio-derived products, which appear as an interesting economic opportunity in national and global markets. Thus, this study attempts to highlight the recent advances in analytical tools used in detection of secondary metabolites, which can be useful as bioproducts. It also emphasizes the potential avenues to be explored in Brazilian biodiversity, known for its rich chemical diversity.