Despite the recently introduced concept of Combinatorial Chemistry of organic molecules achieved via the development of modern automatic synthetic methods, tropical forests continue to be the main source of leading new bioactive compounds in drug discovery. The main focus of the pharmaceutical industry has been on microorganisms as a source for new drugs. However, at the beginning of the 1960's the discovery of the anticancer drugs, vincristine and vinblastine, from Catharanthus roseus (Apocynaceae) and podophyllotoxin from Podophyllum peltatum (Berberidaceae) has highlighted the importance of plants as the raw materials in the search for natural drugs. Many pharmaceutical companies have since then demonstrated enormous interest in plant species as a source for new useful compounds. This process resulted in the development of high throughput screening techniques to find new drugs or leading compounds, which, after minor structural changes, could give rise to new drugs in a more efficient way (more rapidly and with reduced costs).

       From 1960 to 1998 the NCI-USA screened thousands of plant-derived extracts for antitumoral activity in the in vitro and in vivo assays based on three cell lines. This effort resulted, for example, in the discovery of taxol (paclitaxel and docetaxel) and camptothecin (topotecan and irinotecan). In the 70's the discovery of artemisinin, a potent drug to treat cerebral malaria, isolated from Artemisia annua, a Chinese medicinal plant, was another important event in the search for plant-derived drugs and confirmed the potential of secondary metabolites as leading new molecules. A five-year International Cooperative Biodiversity Group (ICBG) program was launched in 1993 by NIH-USA, directed at bioprospection in Latin America and Africa aiming to search for compounds to treat or prevent cancer, infectious diseases, including AIDS, cardiovascular diseases, malaria and several parasitic disturbances, among others. Although, ICBG was a collaborative program between the USA and developing countries, it failed to bridge the drug discovery effort and the promotion of social and economic development in biodiversity rich countries. The alternative for the efficient use of the biodiversity as a source for new drugs would be the integrated efforts of the local expertise taking part in all processes involved in bioprospection: sampling, classification/identification, preparation of extracts, bioassay development and bioassay guided-fractionation, chemical characterization, and efficient information storage and handling. The close association with pharmaceutical, cosmetic and agrochemical industries is highly desirable, either at earlier or later stages of the bioprospection initiative, particularly in the compound development phases. The global demand to preserve the biodiversity in developing countries has been widely cited as a mean to promote economic development through incentives for sustainable uses of the genetic resources. Recently, several efforts by governmental and non-governmental organizations have attempted to initiate bioprospection programs in Brazil. In order to discover new drugs, it is certainly necessary to evaluate large amounts of extract or candidate compounds in preliminary biological or biochemical assays that are predictive of a corresponding and specific activity in the target organism. The probability of finding positive hits of bioactive compounds depends on the number of samples screened, the diversity of samples and the diversity of assays.

       A pilot project for bioprospecting plant species in the State of São Paulo has been pioneered within the Biota-FAPESP program, successfully demonstrating the viability of this integrated approach. The aim is now to expand this initiative, widening the scale of organisms and bioassays involved, and integrating all research groups interested in this effort. This is the scope of the Rede Biota de Bioprospecção e Bioensaios-RedeBio.

       In order to establish a competitive bioprospecting program in the State of São Paulo to screen thousands of samples, it will be necessary to adapt the local expertise to the new needs. It is true that this network will not be able to compete with developed countries in the search for new drugs, especially those related to "developed countries diseases". Nevertheless, we can use the large experience of our research groups to create similar strategies to solve regional problems, especially to combat orphan diseases like leishmaniasis, Chagas, malaria and other tropical diseases. In addition, the chemical diversity of species from tropical forests is still a useful source of new potential anticancer, antioxidant, antifungal, anti-inflamatory or antibiotic compounds. Thus, these targets must also be taken into consideration, due to the potential benefits that a new discovery in these areas could bring to the Brazilian economy.

       Biota-FAPESP, which was initially designed to map the biodiversity of São Paulo State, represents the proper host for this bioprospecting program, bringing together the contributions of the scientific community as well as the pharmaceutical, cosmetic and agrochemical industries. With this cooperative program, called -RedeBio-, we will substantiate the rational use and exploitation of biodiversity and help our country to improve its competitiveness in the global economy.

       The State of São Paulo State has several research groups working on all areas which are important for a successful bioprospection program, with remarkable experience and proved competences. The Biota Program has brought together a large group of researchers involved in the taxonomical knowledge of our biodiversity. We have many groups working in isolation/purification and structure elucidation of natural metabolites; others with large experience in pharmacology with established in-vitro and in-vivo bioassays; others with excellent facilities and expertise for the rapid identification and characterization of compounds in crude extracts (e.g. NMR, crystallography, mass spectrometry, etc…). Nevertheless, there is a strong need for a better integration of these competences within the common goal of achieving the desired applications for our biodiversity.

       The goal of RedeBio is to organize a network of researchers and laboratories with the objective of establishing the basis for the sustainable use of our biodiversity.

Objectives

       This Call for Proposals is open for applications of research groups willing to work within the frame of a network focused within the following topics:

- Standardized collection of biological samples (plants, microorganisms., marine species, insects, etc…) and pre-processing of raw materials for the subsequent preparation of extracts.

- Creation of a bank of extracts and pure compounds from plants, microorganisms, marine organisms and other natural sources, with the required automation and data management facilities.

- Natural Products Chemistry: Preparation of standardized extracts, fractionation and purification.

- Characterization of promising extracts/compounds (NMR, Crystallography, LC/GC-MS, etc…) - Screening of extracts with existing in-vitro and in-vivo bioasssays

- Development of new bio-assays, particularly those adequate for High-Throughput Screening using small sample volumes.

- Pharmacology and toxicology of promising bioactive extracts or compounds.

- Synthesis of bioactive natural products and their derivatives.

- Medicinal chemistry and drug design applied to the development of promising compounds.

- Development of a database structure for the data processing of the program.

- Other related areas.