Gold conjugates and biomolecules for the treatment of cutaneous Leishmaniasis

• Grant number: 24/09174-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Camilla Abbehausen
• Grantee: Giovanna Bruna Braga
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/02618-0 - Design of novel metallodrugs and innovative administration routes for Leishmaniasis treatment, AP.PNGP.PI

Abstract

Leishmaniasis is a parasitic disease caused by Leishmania spp., a kinetoplastid protozoa, transmitted to mammals through the bite of a female sandfly. According to the World Health Organization, it is endemic in 88 countries and affects 12 million people worldwide, and it is classified as one of the most neglected tropical diseases. Treatment options have high toxicity, resistance problems, high costs, complicated modes of administration, and prolonged treatment regimens that can cause several side effects. Gold organometallic complexes are thiophilic agents known for their anti-inflammatory properties and have proven promising as anticancer and antiparasitic agents. Our research group has been investigating metal complexes as alternative treatments for leishmaniasis, especially gold organometallics. Reports suggest that the mechanism of antiparasitic action involves the induction of oxidative stress, which can occur both by the direct production of ROS and by the indirect accumulation of these species due to the inhibition of Trypanothione Reductase (TR) and mitochondrial damage. Our group detected compounds with excellent performance in vitro and in vivo. Mechanistically, the compounds increase membrane permeabilization and induce ultrastructural modification in mitochondria. In the main project (2022/02618-0), we propose to improve targeting by peptide bioconjugation. Binding biomolecules to metal complexes (bioconjugation) can provide selectivity for inter- or intracellular targets and decrease off-target interactions. Our group wants to develop means to bioconjugate metal complexes to a peptide with a high affinity for TR. However, we have found that the conjugation changes chemical properties considerably.