Computational studies on N-myristoyltransferase enzyme from Plasmodium falciparum and its inhibitors as antimalarial agents

• Grant number: 15/21272-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2016
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Rafael Victorio Carvalho Guido
• Grantee: Mariana Lopes Garcia
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

The research project investigate an extremely sensitive area of human health, related to tropical diseases that affect millions of people worldwide, especially in poorest regions. The project aims at the identification of the structural determinants underlying the biological activity of a series of P. falciparum N-miristoiltransferase inhibitors as antimalarial drug candidates. Knowledge of these determinants will allow the design of new chemotherapeutic agents with optimized biological properties. Potent benzo[b]thiophene derivatives are candidates for new antiparasitic agents with high potential for clinical development.This proposal incorporates medicinal chemistry and molecular modeling studies by integrating ligand- and structure-based drug design (LBDD and SBDD, respectively) strategies. The project will be developed at Medicinal Chemistry and Computational Laboratory and Centre for Research and Innovation in Biodiversity and Drug (CIBFar-CEPID / FAPESP), from the São Carlos Institute of Physics - USP. The CIBFar laboratories have complete infrastructure to perform all the steps proposed in this master's project.The group was part of the World Health Organization (WHO, World Health Organization) as a World Reference Center for Medicinal Chemistry for Chagas Disease, and also the National Institutes Program of Science and Technology MCT / MS / CNPq / FAPESP, as National Institute for Structural Biotechnology and Medicinal Chemistry in Infectious Diseases (INBEQMeDI), which show the quality of the group in the area of infectious diseases and the importance of this project within the context of the initiatives against tropical diseases of enormous global impact.

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)

Academic Publications

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

GARCIA, Mariana Lopes. Computational studies on Plasmodium falciparum N-myristoyltransferase enzyme and its inhibitors as antimalarial drug candidates. 2017. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.