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Applications of new desferrioxamine derivatives with high cell permeability

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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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)
CARVALHO, RODRIGO R. V.; PERES, TANARA V.; LIRIA, CLEBER W.; MACHINI, M. TERESA; ASCHNER, MICHAEL; ESPOSITO, BRENO P. Conjugates of desferrioxamine and aromatic amines improve markers of iron-dependent neurotoxicity. BIOMETALS, JAN 2021. Web of Science Citations: 0.
ESPOSITO, BRENO PANNIA; MARTINS, AIRTON CUNHA; DE CARVALHO, RODRIGO RODRIGUES VICTOR; ASCHNER, MICHAEL. High throughput fluorimetric assessment of iron traffic and chelation in iron-overloadedCaenorhabditis elegans. BIOMETALS, v. 33, n. 4-5, p. 255-267, OCT 2020. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.