Evaluating Metabolic Effects of Synthetic Terpenes on Plasmodium falciparum for New Drug Development

• Grant number: 23/12343-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date until: November 01, 2023
• End date until: October 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Alejandro Miguel Katzin
• Grantee: Maurício Mazzine Filho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Malaria, caused by Plasmodium falciparum parasites, constitutes a substantial public health concern, particularly in developing nations. While existing medications hold the capacity to combat the disease, the emergence of Plasmodium resistance to these drugs has posed a formidable challenge, prompting the exploration for novel antimalarial agents. Drawing upon the discoveries of our research team, diverse natural terpenes, including geraniol, nerolidol, and limonene, have exhibited both in vitro and in vivo antimalarial effects. These compounds have manifested multifaceted impacts on isoprenoid metabolism. Moreover, geraniol has demonstrated inhibition of a parasitic prenol kinase, an enzyme recently identified by our research group. This inhibition increases the effectiveness of several other antimalarials targeting isoprenoid biosynthesis, such as fosmidomycin and clindamycin. This project's core objective involves the exploration of synthetic terpenes' potential as modulators of isoprenoid metabolism and inhibitors of the prenol kinase enzyme of P. falciparum. Additionally, the project seeks to enhance the antimalarial efficacy of these compounds through structural refinements and to assess their synergistic effects with other drugs. The overarching aim is to contribute significantly to the advancement of innovative therapeutic approaches for combating malaria.