Structural Biology and Medicinal Chemistry studies toward the discovery and design of new agrochemicals

Abstract

Sustainable development exhibits as main feature the use of scientific knowledge to generate technological innovation to meet human needs while preserving the environment. In this context, the environmental benefits obtained from the production and use of sugarcane derivatives boost the development of methods and strategies to enhance the generation of bioenergy. However, the incidence and severity of plant diseases, such as leaf scald, hinder the productivity of sugarcane crops. Sugarcane leaf scald is a widespread and devastating disease caused by the bacteria Xanthomonas albilineans. The disease has a dramatic impact on crop productivity, including reduced yields and drop in quality of the juice. Currently, there is no chemical or biological treatment for disease control. Therefore, there is an urgent need for new effective and selective agrochemicals with low cost and environmental impact. This project is based on basic science research with the main goal of advancing the fundamental knowledge on the structure and function relationships of relevant molecular targets of the X. albilineans, however, the results have great potential for innovation and technology transfer. The goals of the project will be achieved on the basis of the suitable infrastructure, skills and organization of our multidisciplinary research group established at the Center for Structural Molecular Biotechnology - CBME (CEPID-FAPESP), the National Science and Technology Institute of Medicinal Chemistry and Structural Biotechnology for Infectious Diseases - INBEQMeDI (INCT-CNPq-FAPESP) and the World Health Organization (WHO) Medicinal Chemistry Center for Chagas' disease established at the Institute of Physics São Carlos (IFSC), University of São Paulo (USP). The doctorate activity plan, associated with the Young Investigators grant entitled "Discovery and Development of New Antibacterial Agents as Agrochemicals for Sugarcane Cultures: Biological Screening, Medicinal Chemistry and Structural Biology" (2011/08042-9), includes studies on basic and applied science research based on modern structural biology (e.g., gene cloning, protein expression and purification, protein crystallography) and medicinal chemistry (e.g., biological assays and screening of bioactive compounds, mechanism of action, structure-based drug design) strategies for the development of bioactive compounds as inhibitors of benzoate-CoA ligase (BCL) enzyme from X. albilineans. Potent and selective inhibitors of the enzyme are new agrochemical candidates to control the leaf scald disease. (AU)