Nanoparticle-assisted drug delivery of Vitamin B6 pathway inhibitors in malaria

• Grant number: 18/08820-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2018
• Effective date (End): May 31, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal researcher: Carsten Wrenger
• Grantee: Arne Kruger
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/26722-8 - Drug discovery against human infectious diseases, AP.TEM

Abstract

Protozoan parasites are highly distributed among tropical countries, especially South-America, Sub-Saharan Africa and South-East Asia. Among these parasites, Plasmodium is the causative agent of malaria, the most devastating parasitic disease. Due to inefficient treatments and the fast-developing parasites, the existing drugs are losing efficacy because more and more resistances are occurring rapidly. Therefore, it is necessary to increase research in the fields of drug discovery, drug target efficacy and drug delivery. It is highly recommended to focus on drug targets that are specific for the pathogen to reduce side effects on the human. Hence, in this doctoral application, we will focus on compounds inhibiting the vitamin B6 biosynthetic pathway of Plasmodium falciparum, the species which causes severe malaria and is responsible for most of the malaria cases in Sub-Saharan Africa. In a first attempt, compounds will be designed to address the vitamin B6 biosynthetic enzymes Pdx1 and /or Pdx2 and inhibit their activity. Following this, the compounds will be tested on in vitro and in vivo studies using cell culture and mice experiments, respectively. After evaluating the compound's efficacy and biocompatibility, nano-technological approaches will be used to improve the efficacy of the treatment. For that, nanoparticles (NPs) will be used to modulate the pharmacological properties of the compounds, facilitating the delivery and protecting against degradation inside the body. With this, we aim to develop a biocompatible, affordable, and highly potent drug delivery system for an effective treatment of malaria.

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)

PILLAT, MICHELI MAINARDI; KRUGER, ARNE; FERREIRA GUIMARAES, LARA MENDES; LAMEU, CLAUDIANA; DE SOUZA, EDMARCIA ELISA; WRENGER, CARSTEN; ULRICH, HENNING. Insights in Chloroquine Action: Perspectives and Implications in Malaria andCOVID-19. Cytometry Part A, v. 97, n. 9 AUG 2020. Web of Science Citations: 0.

KRUGER, ARNE; ZIMBRES, FLAVIA M.; KRONENBERGER, THALES; WRENGER, CARSTEN. Molecular Modeling Applied to Nucleic Acid-Based Molecule Development. BIOMOLECULES, v. 8, n. 3 SEP 2018. Web of Science Citations: 4.