Discovery and Design of Folate Synthesis Inhibitors as Agrochemicals Candidates for Sugar Cane Culture

• Grant number: 13/04737-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2013
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Rafael Victorio Carvalho Guido
• Grantee: Renata Vieira Bueno
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 11/08042-9 - Discovery and development of new antibacterial agents as agrochemicals for sugarcane cultures: biological screening, medicinal chemistry and structural biology, AP.BIOEN.JP
• Associated scholarship(s): 16/16038-5 - Exploring compound screening strategies to identify inhibitors of N5, N10: methylenetetrahydrofolate dehydrogenase-cyclohydrolase from Xanthomonas albilineans, BE.EP.DR

Abstract

Sugar cane stands out as one of the main renewable energy sources in the search for clean and sustainable energy in Brazil. However, sugar cane cultures are threatened by several factors, among them, 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. The absence of chemical or biological agents against the disease boosts the research and development of new bioactive molecules as effective pesticides. The folates biosynthesis is essential for bacterial replication and, because of that, widely investigated for the development of antibiotics. In this metabolic pathway, the key enzyme XaFolD is an attractive molecular target for selective inhibition. On the basis on that, the proposal aims at the integration of experimental and computational strategies toward the design of new bioactive compounds. The main goal of the project is the structural determination of the FolD enzyme from X. albilineans as well as the discovery and development of potent and selective inhibitors as new agrochemical candidates for sugar cane. To achieve these goals, integrated Structural Molecular Biology (e.g., cloning, protein expression, crystallization, data collection, crystallographic complexes) and Medicinal Chemistry (e.g., enzymatic assays, biological screening, biological properties determination, molecular modeling) strategies will be employed.The doctorate activity plan is closely 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), currently under development at the Medicinal Chemistry and Computational Lab and Center for Structural Molecular Biotechnology of the Physics Institute of São Carlos.Our research group is associated with World Health Organization (WHO) as the Medicinal Chemistry Center for Chagas' disease and the National Science and Technology Institute of Medicinal Chemistry and Structural Biotechnology for Infectious Diseases - INBEQMeDI (INCT-CNPq-FAPESP), which highlight the quality of the group in the infectious diseases field as well as the importance of this proposal as a novel initiative toward the development of bioactive compounds for the safe control of sugar cane leaf scald disease.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GARCIA, MARIANA L.; DE OLIVEIRA, ANDREW A.; BUENO, RENATA, V; NOGUEIRA, VICTOR H. R.; DE SOUZA, GUILHERME E.; GUIDO, RAFAEL V. C.. QSAR studies on benzothiophene derivatives as Plasmodium falciparum N-myristoyltransferase inhibitors: Molecular insights into affinity and selectivity. Drug Development Research, v. 83, n. 2, p. 21-pg., 2020-02-11. (15/07005-3, 15/21272-4, 13/07600-3, 13/04737-8)

GARCIA, MARIANA L.; DE OLIVEIRA, ANDREW A.; BUENO, V, RENATA; NOGUEIRA, VICTOR H. R.; DE SOUZA, GUILHERME E.; GUIDO, RAFAEL V. C.. QSAR studies on benzothiophene derivatives as Plasmodium falciparum N-myristoyltransferase inhibitors: Molecular insights into affinity and selectivity. Drug Development Research, FEB 2020. (13/04737-8, 13/07600-3, 15/07005-3, 15/21272-4)

POLITI, FLAVIO AUGUSTO SANCHES; BUENO, RENATA VIEIRA; ZEOLY, LUCAS ANDRE; FANTATTO, RAFAELA REGINA; ELOY, JOSIMAR DE OLIVEIRA; CHORILLI, MARLUS; COELHO, FERNANDO; GUIDO, RAFAEL VICTORIO CARVALHO; CHAGAS, ANA CAROLINA DE SOUZA; FURLAN, MAYSA. Anthelmintic activity of a nanoformulation based on thiophenes identified in Tagetes patula L. (Asteraceae) against the small ruminant nematode Haemonchus contortus. Acta Tropica, v. 219, JUL 2021. (14/50926-0, 13/04737-8, 13/03493-8, 11/08042-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BUENO, Renata Vieira. Structural and functional studies of the enzyme N5, N10 -methylenetetrahydrofolate dehydrogenase-cyclohydrolase of Xanthomonas albilineans applied to the discovery of inhibitor candidates for the treatment of leaf scald. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.