| Grant number: | 18/19684-0 |
| Support type: | Regular Research Grants |
| Duration: | March 01, 2019 - December 31, 2021 |
| Field of knowledge: | Health Sciences - Pharmacy - Pharmacognosy |
| Principal researcher: | Breno Pannia Esposito |
| Grantee: | Breno Pannia Esposito |
| Home Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract
Iron overload is a debilitating condition for patients, leading to decreased quality of life. At the same time, iron is a crucial nutrient also for parasites and tumor cells. Iron chelators are high affinity molecules that display several possibilities of clinical use: (i) reducing metal overload; (ii) delivering toxic metals to selected targets; (iii) scavenging essential metals from said targets. Desferrioxamine (DFO), a bacterial siderophore, was the first clinically approved iron chelator, displaying high affinity for Fe(III). However, its use is hampered since it has low cell permeability and low gastrointestinal absorption. Our laboratory developed two DFO derivatives with high cell permeability, DFO-caffeine (DFCAF) and DFO-triphenylphosphonium (TPP-DFO), aimed at the blood-brain barrier and mitochondria, respectively. In this project, we propose to follow up with the studies for both conjugates, by studying their permeability profiles in artificial membranes (PAMPA systems), seeking new pharmacological applications against neglected diseases (anti-leishmanial, anti-chagasic, anti-malarial, anti-tuberculosis and anti-leprosy) based on their ability to disturb iron metabolism, and conducting in vivo experiments in models of iron overload. To that end, national and international collaborations with experts in each area have been established. (AU)
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