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Chemistry: a key science to fight neglected diseases/Quimica: ciencia central para combater doencas negligenciadas.

Over the past century, chemical and pharmaceutical industries have made substantial strides in the development of new pharmaceuticals for a range of human diseases. Discovering and developing new drugs are part of a costly process that involves not only the search for new drug candidates, but also the performance of clinical trials. It is not uncommon to find reports of costs reaching US$ 500 million--and even US$ 1 billion--engaging multidisciplinary teams for periods of 10 or 15 years. To a large extent, these costs are borne by consumers in richer countries. In contrast, diseases that predominantly affect residents of poorer nations tend to be left out of the modern process of drug discovery. Moreover, most of the world population stricken by these illnesses is incapable of supporting the costs involved in developing the drugs they need. Because these infirmities, with few exceptions, have been ignored by those in charge of research programs, both in the public and private sectors, they have been referred to as neglected diseases. On its website, the World Health Organization categorizes 14 health conditions as "tropical diseases," owing to their strict or predominant occurrence in the tropics. Most are infectious illnesses such as leishmaniasis, dengue fever, malaria, and Chagas' disease, which largely affect poor populations.

The drugs available for treating these conditions are regrettably scarce. In many regions, for instance, first-choice therapy for late-stage human African trypanosomiasis (HAT, or sleeping sickness) is still based on melarsoprol, an arsenic-derived drug developed in the late 19th century that can lead to fatal encephalopathy in 5% of patients. Another example is the unavailability of treatments, with the exception of the prolonged use of genotoxic drugs, for Chagas' disease, which affects a significant proportion of children.

Expansion of the arsenal of drugs for neglected diseases is therefore badly needed. The current situation calls for extensive studies and significant improvement in research support policies in the field of neglected diseases, despite the considerable body of scientific investigations focusing on the biology, immunology, and genetics of the parasites responsible for these conditions. Both in the university and the pharmaceutical industry, chemistry continues to drive the discovery of novel drugs. In the universities, chemists are contributing with studies targeted at obtaining compounds to fight neglected diseases. In this endeavor, the diverse areas of chemistry are increasingly teaming up to conduct studies so as to further clarify the structure-activity relationship of organic compounds; concurrently, increased knowledge is gained on the effects of small molecules on biological processes, thanks to the growing interaction between chemistry and biology. Today, chemists are no longer restricted to the realm of covalent bonds, but have also been exploring the territory of supramolecular interactions, constructing supermolecules that exhibit specific properties such as auto-assembly, molecular recognition, transformation, transport, and signaling [1]. In this new field, theoretical chemistry is crucial for the study of physicochemical properties, relying on quantum chemistry to anticipate the behavior or molecules and, consequently, their biological activity under different reactivity conditions [2]. Chemists still find their primary source of inspiration in natural products, as the wide range of structures exhibited by these compounds makes nature an inexhaustible source of new products--a range of diversity that can astonish even the most resourceful chemist. No wonder, therefore, that nature's vast richness keeps continuously yielding useful products--in limitless numbers and for every conceivable purpose.

Durante o seculo passado, industrias quimicas e farmaceuticas fizeram grandes progressos no desenvolvimento de novos farmacos para o tratamento de muitas doencas. O processo de descoberta e desenvolvimento de novos medicamentos, que engloba pesquisas para encontrar novos candidatos a farmacos e ensaios clinicos, e muito dispendioso. Nao e raro encontrar referencias sobre custos que variam de US$ 500 milhoes a US$ 1 bilhao, envolvendo a dedicacao de equipes multidisciplinares por periodos que alcancam de dez a quinze anos. Em grande medida, esses custos sao bancados pelos consumidores de paises mais ricos. Por outro lado, doencas que afetam predominantemente habitantes de nacoes mais pobres tendem a ser deixadas a margem do processo moderno de descoberta de drogas. Alem disso, os atingidos sao incapazes de arcar com os custos do desenvolvimento desses farmacos. Tais doencas tem sido ignoradas, com algumas excecoes, pelos supervisores de programas de pesquisas do setor publico ou privado e, por isso, sao muitas vezes designadas como doencas negligenciadas. O site da Organizacao Mundial da Saude lista 14 enfermidades na categoria "doencas tropicais", de ocorrencia exclusiva ou majoritaria nos tropicos. A maioria delas sao doencas infecciosas que afetam principalmente populacoes pobres, como leishmaniose, dengue, malaria e doenca de Chagas.

Os medicamentos existentes para trata-las sao lamentavelmente poucos. Por exemplo, a terapia de primeira escolha destinada a fase 2 da tripanossomiase humana africana (HAT, ou doenca do sono) em muitas regioes ainda e o melarsoprol (desenvolvido no final do seculo 19), que, por ser derivado de arsenio, provoca encefalopatia fatal em 5% das pessoas tratadas. Outro exemplo: o tratamento prolongado com drogas genotoxicas e a unica escolha para a doenca de Chagas, em que uma proporcao significativa dos pacientes e constituida de criancas.

E urgente, portanto, a necessidade de ampliar o arsenal de medicamentos para as doencas negligenciadas. A situacao exige amplas pesquisas e melhoria significativa da politica de apoio a investigacao na area das doencas negligenciadas, apesar do ja consideravel volume de trabalhos cientificos relacionados a biologia, imunologia e genetica dos parasitas que causam muitas dessas enfermidades. Tendo-se em vista a situacao apresentada, o papel da quimica na academia e na industria farmaceutica continua a ser o de propulsor decisivo para a descoberta de novas drogas. Na academia, os quimicos contribuem com estudos voltados a obter compostos para combater doencas negligenciadas. Nesse campo, cada vez mais, as varias areas da quimica se associam e desenvolvem estudos visando o entendimento da relacao estrutura--atividade dos compostos organicos; simultaneamente a interacao entre a quimica e a biologia permite compreender melhor os efeitos de pequenas moleculas em processos biologicos. Alem disso, o quimico de hoje esta indo alem das ligacoes covalentes, enveredando-se tambem no entendimento das interacoes supramoleculares, criando supermoleculas que apresentam propriedades especificas, tais como automontagem, reconhecimento molecular, transformacao, transporte e sinalizacao [1]. Nesse contexto, a quimica teorica desempenha um papel de extrema importancia no estudo de propriedades fisico-quimicas, utilizando a quimica quantica para prever o comportamento de moleculas e, consequentemente, sua atividade biologica em diversas situacoes de reatividade [2]. Os produtos naturais sao a maior fonte de inspiracao para os quimicos e abrangem uma variedade tao grande de estruturas, que permitem ver na natureza uma fonte inesgotavel de novos produtos. Essa diversidade faz surpreender ate mesmo os profissionais mais criativos da quimica. Nao e de estranhar, portanto, que dentre toda essa riqueza seja possivel encontrar produtos uteis para todos os fins, e em abundancia.

Adilson Beatriz (UFMS)

Editor, Orbital

Denis Pires de Lima (UFMS)

Associate Editor, Orbital

References

[1] Araki, K.; Toma, H. E. Quimica Nova 2002, 25, 962.

[2] dos Santos, R.; Lacerda-Junior, V. de Castro, E.; Balthar, V.; Greco, S. Orbital 2009, 1, 273. Available from: http://www.orbital.ufms.br/index.php/dqi/article/view/105/29
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Title Annotation:Editorial
Author:Beatriz, Adilson; de Lima, Denis Pires
Publication:Orbital: The Electronic Journal of Chemistry
Date:Oct 1, 2009
Words:1172
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