Dissection of the lipoic acid metabolism as druggable target in Malaria

• Grant number: 17/26358-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2018
• End date: June 30, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Carsten Wrenger
• Grantee: Sun Liu Rei Yan
• Host 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

The Malaria parasite Plasmodium falciparum possesses organelles such as mitochondrion and the chloroplast-like compartment named apicoplast which is absent in the human host. Interference with metabolic pathways present in the latter one has been proven be lethal for the parasite. This doctoral research project aims to identify antibacterial compounds by targeting the lipoic acid metabolism of S. aureus utilizing two different approaches: the lipoic acid salvage pathway will be addressed by suicide substrates mimicking natural substrates, resulting in generation of nonfunctional cofactors that poison all cofactor dependent enzymes. A second approach intends to identify enzyme inhibitors targeting lipoic acid biosynthesis enzymes. The results may not only validate enzymes of the lipoic acid biosynthesis and salvage pathway as attractive targets for novel therapeutic approaches, but also provide bioactive molecules for further drug development. The discovery of drugs interfering with the lipoic acid metabolism in Malaria possesses a novel drug target which is restricted to the parasite. (AU)

Scientific publications

(5)

(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)

LINZKE, MARLEEN; YAN, SUN LIU REI; TARNOK, ATTILA; ULRICH, HENNING; GROVES, MATTHEW R.; WRENGER, CARSTEN. Live and Let Dye: Visualizing the Cellular Compartments of the Malaria Parasite Plasmodium falciparum. Cytometry Part A, v. 97, n. 7, SI, NOV 2019. (12/50880-4, 17/03966-4, 15/26722-8, 14/23330-9, 17/26358-0, 12/50393-6)

REI YAN, SUN LIU; WAKASUQUI, FELIPE; DU, XIAOCHEN; GROVES, MATTHEW R.; WRENGER, CARSTEN. Lipoic Acid Metabolism as a Potential Chemotherapeutic Target Against Plasmodium falciparum and Staphylococcus aureus. RONTIERS IN CHEMISTR, v. 9, p. 7-pg., 2021-11-04. (17/26358-0, 15/26722-8, 17/03966-4)

REI YAN, SUN L.; WAKASUQUI, FELIPE; WRENGER, CARSTEN. Point-of-care tests for malaria: speeding up the diagnostics at the bedside and challenges in malaria cases detection. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 98, n. 3, NOV 2020. (15/26722-8, 17/26358-0)

RIBEIRO, GIOVANE DE JESUS GOMES; YAN, SUN LIU REI; PALMISANO, GIUSEPPE; WRENGER, CARSTEN. Plant Extracts as a Source of Natural Products with Potential Antimalarial Effects: An Update from 2018 to 2022. PHARMACEUTICS, v. 15, n. 6, p. 19-pg., 2023-06-01. (18/15549-1, 18/18257-1, 20/04923-0, 17/26358-0, 15/26722-8)

LINZKE, MARLEEN; YAN, SUN LIU REI; TARNOK, ATTILA; ULRICH, HENNING; GROVES, MATTHEW R.; WRENGER, CARSTEN. Live and Let Dye: Visualizing the Cellular Compartments of the Malaria Parasite Plasmodium falciparum. Cytometry Part A, v. 97, n. 7, p. 12-pg., 2019-11-18. (17/03966-4, 12/50880-4, 14/23330-9, 12/50393-6, 17/26358-0, 15/26722-8)