From Medicinal Chemistry to Human Health: Current Approaches to Drug Discovery for Cancer and Neglected Tropical Diseases

ABSTRACT Scientific and technological breakthroughs have compelled the current players in drug discovery to increasingly incorporate knowledge-based approaches. This evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. As a result, ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry's striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates - in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety. To that end, the Laboratório de Química Medicinal e Computacional (LQMC) of the Universidade de São Paulo has developed forefront research on highly prevalent and life-threatening neglected tropical diseases and cancer. By taking part in global initiatives for pharmaceutical innovation, the laboratory has contributed to the advance of these critical therapeutic areas through the use of cutting-edge strategies in medicinal chemistry.

Setting research priorities by applying the combined approach matrix.

Background & objectives: Priority setting in health research is a dynamic process. Different organizations and institutes have been working in the field of research priority setting for many years. In 1999 the Global Forum for Health Research presented a research priority setting tool called the Combined Approach Matrix or CAM. Since its development, the CAM has been successfully applied to set research priorities for diseases, conditions and programmes at global, regional and national levels. This paper briefly explains the CAM methodology and how it could be applied in different settings, giving examples and describing challenges encountered in the process of setting research priorities and providing recommendations for further work in this field. Methods: The construct and design of the CAM is explained along with different steps needed, including planning and organization of a priority-setting exercise and how it could be applied in different settings. Results: The application of the CAM are described by using three examples. The first concerns setting research priorities for a global programme, the second describes application at the country level and the third setting research priorities for diseases. Interpretation & conclusions: Effective application of the CAM in different and diverse environments proves its utility as a tool for setting research priorities. Potential challenges encountered in the process of research priority setting are discussed and some recommendations for further work in this field are provided.

O Brasil e a medicina tropical / Brazil and tropical medicine

Säo feitas consideraçöes sobre o papel das endemias tropicais no desenvolvimento da sociedade brasileira. Aborda-se a atualidade das pesquisas que tratam da temática das doenças infecciosas. Comparando o significado para o primeiro mundo, conclui-se pela necessidade de estimular as pesquisas nessa área e de prestigiar os periódicos nacionais destinados a divulgá-las.

Saúde, Medicina e Nutriçäo nos trópicos: uma introduçäo / Health, Medicine and Nutrition in the tropics: an introduction

Aborda o conceito de saúde desde a concepçäo simplista, ou seja, "ausência de doenças" até concepçöes muito abrangentes como a adotada pela Organizaçäo Mundial de Saúde, que define "um estado completo de bem estar físico, mental e social e näo apenas a ausência de doença e enfermidade". O conceito de Medicina Tropical difere conforme o país ou regiäo. Nos países europeus e nos Estados Unidos a chamada "Medicina Tropical" praticamente se confunde com a parasitologia e a entomologia. A nutriçäo, nos países dos trópicos, apresenta fatores relevantes, como por exemplo as condiçöes econômicas e sociais. É certo que fatores educacionais, culturais e ecológicos säo também importantes, mas certamente näo säo os principais. A desigualdade na distribuiçäo de renda, a desnutriçäo e os baixos níveis de saúde säo fatores do subdesenvolvimento da grande maioria dos países de clima tropical.(AMN)