Design of new antibiotics based in the fragment based drug discovery technique from the inhibition of vitamin biosynthesis in Mycobacterium tuberculosis

• Grant number: 13/26242-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2014
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Microbiology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcio Vinicius Bertacine Dias
• Grantee: Jademilson Celestino dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 10/15971-3 - Structural characterization of enzymes from antibiotic biosynthetic pathways with biotechnological interest, AP.JP

Abstract

Infectious diseases are one serious problems of public health worldwide and are one most import causes of death of human population. Among these diseases, tuberculosis has a pivotal importance, because it is one of the infectious diseases which more decimates people around the world. This event occurs mainly because to the emerging of resistant strains to all medicine in use. Although the known public health problems related to this disease, there is not a strong investment of the pharmaceutical companies in the development of new drugs. Thus, the research using public funding represents an important role in the research and development of new drugs. Among the strategies, the discovery of inhibitors for the enzymes from biosynthesis of vitamins has already been largely investigated in Mycobacterium tuberculosis. The biosynthetic pathways of folate and biotin have target enzymes that can be used in the design of new antibiotics against Mycobacterium tuberculosis. At moment, there is not any antibiotic targeting these pathway in the treatment of tuberculosis. In this project, we intent to use the fragment based drug discovery technique to identify small and simple molecules that may be chemically modified to generated new inhibitors targeting the folate and biotin pathway in M. tuberculosis. To apply this approach, a set of biophysical techniques will be applied in the screening and validation of small molecules that may bind on these enzymes active site. (AU)

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)

TORMET-GONZALEZ, GABRIELA D.; WILSON, CAROLINA; DE OLIVEIRA, GABRIEL STEPHANI; DOS SANTOS, JADEMILSON CELESTINO; DE OLIVEIRA, LUCIANA G.; DIAS, MARCIO VINICIUS BERTACINE. An epoxide hydrolase from endophytic Streptomycess hows unique structural features and wide biocatalytic activity. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, v. 76, p. 8-pg., 2020-09-01. (19/10564-5, 18/00351-1, 15/09188-8, 11/06209-3, 14/50249-8, 10/15971-3, 13/26242-0, 14/12727-5)