Desferrioxamine-caffeine: permeability and interaction with biopolymers

• Grant number: 19/19773-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2020
• End date: December 31, 2020
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Breno Pannia Esposito
• Grantee: Julia Tiemy Leal Konno
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Iron overload is a harmful condition for patients, who present a significant decrease in quality of life. Iron chelators are high affinity molecules that present several possibilities for clinical use: (i) metal overload attenuators; (ii) deliverers of toxic metals to selected targets; (iii) hijackers of essential metals of these same targets. Desferrioxamine (DFO), a bacterial siderophore, was the first approved chelator of iron, presenting high affinity and selectivity for iron (III). However, its use is limited because it presents decreased cellular penetration and low gastrointestinal absorption. Our laboratory produced a DFO derivative with high cell permeability, the DFO-caffeine conjugate (DFCAF), designed to penetrate the blood-brain barrier. In this project, we intend to continue the studies with this conjugate, studying its interactions with biopolymers (albumin, apo-transferrin and holo-transferrin) when free or complexed to iron, as well as their permeability in physiological membrane model systems. Comparisons with the starting chelator (DFO) will be performed in parallel. (AU)