Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered clinical trials. However, a significant number of the reported compounds contain problematic functional groups, suggesting that enzyme inhibition could be the result of undesirable side reactions instead of selective binding to IDO1. Here, we describe issues in the employed experimental protocols, review and classify reported IDO1 inhibitors, and suggest different approaches for confirming viable inhibitor scaffolds.

Estratégias para a obtenção de compostos farmacologicamente ativos a partir de plantas medicinais: conceitos sobre modificação estrutural para otimização da atividade

In the present paper we discuss, based in our experience, some experimental procedures which may be employed for isolation of active compounds from medicinal plants. We have also emphasized some insights about the way to obtain more active and selective compounds from natural products through structural modifications oriented for analysis of structure-activity relationships.

Inibidores seletivos de prostaglandina endoperóxido sintase-2 (PGHS-2): nova estratégia para o tratamento da inflamação

Prostaglandins (PG's), produced from arachidonic acid metabolism, are potent mediators of inflammation. Nonsteroidal anti-inflammatory (NSAIDs) exert their effects by inhibition of prostaglandin endoperoxide synthase (PGHS) enzyme, which catalyses the first committed step in arachidonic acid metabolism. Two isoforms of PGHS are known: PGHS-1, constitutively expressed in most tissues, and is responsible for physiological production of PG's. The second isoform, PGHS-2, is induced by cytokines, mitogens and endotoxins in inflammatory cells, and appears to be responsible for the elevated production of PG's during inflammation. With the recent discovery of the inducible PGHS (PGHS-2), the medicinal chemist now possesses a novel target for designing therapeutic agents that could provide suitable anti-inflammatory activity without the ulcerogenic and renal side effects associated with currently available NSAIDs, all of which inhibit both PGHS-1 and PGHS-2.

A influência da Química nos saberes médicos acadêmicos e práticos do século XVIII em Portugal e no Brasil

At the dawn of the eighteenth century chemistry was establishing itself as a physical science on its own right, after a long ancillary relationship with medicine and pharmacy, which had began two centuries before. This association, and the many changes that came along the scientific revolution spread into many walks of life. The Luso-Brazilian world, apparently so removed from the new developments, could not help to be touched by them, as this study shows, in which two contemporary medical authors are analysed. Both were Portuguese who had long lived in Brazil; both practised and wrote extensively on Medicine; both felt the influence of the new times, albeit in quite different ways.

Principais avanços e perspectivas na área de produtos naturais ativos: estudos desenvolvidos no NIQFAR/UNIVALI

This work describes the more promising chemical and pharmacological or biological results obtained with some selected Brazilian medicinal plants, which has been conducted at Núcleo de Investigações Químico-Farmacêuticas (NIQFAR)/UNIVALI in the last five years. It was found that several phytoconstituents exhibit different activities, such as antispasmodic, antiallergic, analgesic, antiinflammatory, antimicrobial and antiviral. Some of them were more potent than some well-known standard drugs used clinically.

Planejamento racional de fármacos baseado em produtos naturais

In the area of drug discovery, natural products represent a myriad of templates for new lead discovery. It is, however, most unlikely that the bioactive principle itself shall become a drug; it is much more likely that a medicinal chemistry project needs to be initiated as soon the potency or selectivity or specificity of the new natural product candidate has been disclosed. Brazil has an enormous biodiversity where just a few has been disclosed. Nevertheless, it urges to initiate a joint collaboration in order to circumvent a major breakdown linking between natural products and medicinal chemistry in this country. This paper is intended to encourage people to follow up one of the most pushing forward enterprise that needs to be settled: the pharmaceutical industry.

Fármacos e fitoterápicos: a necessidade do desenvolvimento da indústria de fitoterápicos e fitofármacos no Brasil

We discuss briefly the development and the present status of medicinal chemistry. In this context, we consider the therapeutic possibilities of the phytotherapy. On the basis of this analysis, the development of the phytopharmaceutical industry in Brazil is shown to be of essential importance for both the university and the Country due to the human and technological resources involved.

A síntese orgânica em fase sólida e seus suportes poliméricos mais empregados

In the last decade we have seen improved a powerfull tool to medicinal chemistry: the Solid Phase Organic Synthesis (SPOS). This metodology can be used to synthesize a large library of compounds in a short time by combinatorial chemistry, where simple chemical substances can be combinated one to each other building a library of complex compounds. In this work we present the solid phase organic synthesis and their advantage upon the tradicional organic synthesis methodology, as well as the main polimers used in the SPOS technique.

Plantas medicinais: a necessidade de estudos multidisciplinares

This paper presents a program emphasizing ethnopharmacological approaches that could allow great success in the study of medicinal plants. The minimum ethnopharmacological research team should consist of a botanist, a chemist and a pharmacologist with each carrying the responsibility for answering in sequential fashion critical questions. The chemical composition and pharmacological properties of the very efficient medicinal plant Croton cajucara were investigated according to ethnopharmacological approaches. The study with this Croton proved to be both efficient and successful. This happy situation was only possible because a multidisciplinary team was involved getting the research done correctly. The ethnopharmacological study involving one other especies Copaifera will be cited.

Produtos naturais para o controle da transmissão da dengue: atividade larvicida de Myroxylon balsamum (óleo vermelho) e de terpenóides e fenilpropanóides

The bioassay-guided fractionation of the hexane extract obtained from the medicinal plant Myroxylon balsamum (red oil) was conducted in preparative thin layer chromatography on silica gel. The obtained fractions and some terpenoids and phenylpropanoids were assayed as larvicidal on third instar Aedes aegypti larvae, NPPN colony. The results indicate that the sesquiterpene nerolidol was the active constituent in the extract and that the sesquiterpenes were more active than the monoterpenes and phenylpropanoids utilized in this study. Lipophilicity seems to be an important property for the activity since the compounds with hydroxyl, carbonyl and methoxyl groups were less active. The results confirm also that essential oils can be a good tool for the control of dengue.

Back to the island of calm: mallorcan human traditional medicine and ethnobotany

This study reveals that a successful ethnobotanical survey can take place still nowadays, even close to one of the hotspots of tourism in the Mediterranean coast. This is the first approach in this field entirely based on interviews with local people in Mallorca. An amount of 235 informants has been inquired from all the 53 municipalities of the island. The data collected have been analyzed from the botanical and ethnographical points of view, and managed using the online platform of our research team (details at www.etnobiofic.cat). The Mallorcan ethnopharmacopoeia includes 255 plant taxa referring more than 150 medicinal use categories. Ethnomedical queries as the one here presented contribute to the knowledge of the traditional use of plants of the island and appreciate the benefits of this knowledge, applied to the present and future of its society.

Back to the island of calm: Mallorcan human traditional medicine and ethnobotany

This study reveals that a successful ethnobotanical survey can take place still nowadays, even close to one of the hotspots of tourism in the Mediterranean coast. This is the first approach in this field entirely based on interviews with local people in Mallorca. An amount of 235 informants has been inquired from all the 53 municipalities of the island. The data collected have been analyzed from the botanical and ethnographical points of view, and managed using the online platform of our research team (details at www.etnobiofic.cat). The Mallorcan ethnopharmacopoeia includes 255 plant taxa referring more than 150 medicinal use categories. Ethnomedical queries as the one here presented contribute to the knowledge of the traditional use of plants of the island and appreciate the benefits of this knowledge, applied to the present and future of its society.

Programa de pesquisa em produtos naturais: a experiência 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.

O ensino de química quântica e o computador na perspectiva de projetos

This paper aims to discuss and reflect about the use of computers in the teaching of Quantum Chemistry. A course on Computational Quantum Chemistry concentrating on Medicinal Chemistry projects was developed for undergraduate and graduate students. The results showed that students got more motivated and involved when there is an articulation between theory and practice. This work presents an alternative way to teach Theoretical Chemistry using projects.

Plantas medicinais: cura segura?

This paper reviews the recent literature on synergism, adulteration and risks of using medicinal plants. The use of copaiba and sacaca plants as well as their adulteration and side effects, are also described. In addition, the new regulations on phytotherapeutic registration in Brazil and Europe are discussed.