Editorial [ Hot Topic: Targets for Development of Drugs Against Orphan Diseases (Guest Editor: Walter Filgueira de Azevedo Jr.) ]

Recent progress in drug discovery has enabled advanced medicines to be developed against a wide variety of human diseases. However, several infectious diseases have been ignored by research programs in both private and public sectors. These neglected diseases, such as tuberculosis, malaria, leishmaniasis, trypanosomiasis and Chagas disease have a devastating impact on the world's poor. Neglected diseases are mainly diseases of the poor in developing countries. As a result, the pharmaceutical industry has no interest in invest on research for drugs against these diseases, since they affect mostly people with no purchasing power. Among neglected diseases tuberculosis (TB) deserves special attention due to impressive numbers of TB cases. It is estimated that approximately one-third of World's population harbour latent TB, which represents a considerable reservoir of bacilli. This present series of reviews is focused on some efforts that have been made in order to identify new targets for development of drugs against neglected diseases. It will be discussed targets such as enzymes of shikimate pathway, purine nucleoside phosphorylase, protein kinases, and InhA (Enoyl Reductase). All studies bring state-of-art research involving multidisciplinary research teams. Recent results that reveal the structural basis for inhibition of several drug targets and the validation of new targets are described. Parasitic protozoa infecting humans have a greatly impact on public health, especially in the developing countries. Several parasites have developed resistance against chemotherapeutic agents, making the research for new drugs a priority. New drugs may be obtained using Protein Kinases (PKs) as potential targets for development of drugs against a variety of diseases. The structural features that are important to design specific inhibitors against these PKs were reviewed by Canduri and collaborators. The main drugs against tuberculosis are isoniazid and rifampicin, which are used in combination with pyrazinamide and others. However, several strains have been proved to be resistant to these drugs. Mutations in the InhA structural gene and the InhA promoter region have been identified in isoniazid-resistant clinical isolates of M. tuberculosis, subsequent studies revealed that the InhA protein is the target for isoniazid. Structural studies of the InhA mutants will help in the development of a new generation of drugs against tuberculosis and they are reviewed by Oliveira and collaborators. Purine nucleoside phosphorylase (PNP) is another target for drugs against neglected disease. It catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. Silva et al review the main applications of this protein as a target for development of drugs. A set of potential targets for drug development are enzymes of shikimate pathway, which is reviewed by Ducati and collaborators. This pathway is of pivotal importance for production of a plethora of aromatic compounds in plants, bacteria, apicoplexan parasites, and fungi. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms, since it is absent in mammals, shikimate pathway enzymes are potential targets for drug development. These enzymes have been identified in Mycobacterium tuberculosis, Plasmodium falciparum, Toxoplasm gondii, and other pathogenic agents. Several structural and activity studies will be reviewed in the present volume.