Modulation of the levels and reactivity of physiological iron by mean of new natural or bifunctional chelators: possible applications in human health

• Grant number: 16/03709-9
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2016
• End date: January 31, 2019
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Breno Pannia Esposito
• Grantee: Breno Pannia Esposito
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Iron overload is harmful for patients who show a significant decrease in quality of life. Simultaneously, iron is also a crucial nutrient for parasites and tumor cells. Iron chelators are high affinity molecules which have different possibilities of clinical use: (i) attenuators of metal overload; (ii) deliverers of toxic metals to selected targets; (iii) sequestrants of essential metals from those targets. Nowadays, multiple pharmacological target strategies (molecules capable of interfering with more than one biological process) have been favored. In this project, the objective is to (a) derivatize clinically used chelators as bifunctional molecules (anti-leishmanial and anti-neurodegenerative), and (b) explore natural molecules, especially of marine origin, for the activities i - iii above. With this, we hope to contribute to the diversification of therapies of iron overload, infections, tumors and neurodegeneration. (AU)

Scientific publications

(8)

(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)

SIHN, LUCA MICHAEL; DE MELO, FERNANDO MENEGATTI; TOMA, HENRIQUE EISI; PIRES SERRANO, SILVIA HELENA; ESPOSITO, BRENO PANNIA. A new ferrous diflunisal complex and its effects on biopools of labile iron. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, v. 51, p. 65-72, 2019. (16/03709-9, 13/24725-4)

ALTA, ROXANA Y. P.; VITORINO, HECTOR A.; GOSWAMI, DIBAKAR; LIRIA, CLEBER W.; WISNOVSKY, SIMON P.; KELLEY, SHANA O.; MACHINI, M. TERESA; ESPOSITO, BRENO P.. Mitochondria-penetrating peptides conjugated to desferrioxamine as chelators for mitochondrial labile iron. PLoS One, v. 12, n. 2, FEB 8 2017. (16/03709-9, 11/50318-1, 12/09068-4)

CORREIA, LUCAS ANTONIO ARIAS; GARCIA, RODRIGO SANTOS; REAL, CAROLINE CRISTIANO; UZUELI, DANIEL HENRIQUE; SA, ULISSES LACERDA DE FIGUEIREDO; MARQUES, FABIO LUIZ NAVARRO; COLNAGO, LUIZ ALBERTO; ESPOSITO, BRENO PANNIA. Development of a platform for the production of multiple modal chelating and imaging agents using desferrioxamine and bovine albumin as a model. CHEMICAL PAPERS, v. 75, n. 3, p. 7-pg., 2020-09-30. (16/03709-9, 17/16379-0)

CORREIA, LUCAS ANTONIO ARIAS; GARCIA, RODRIGO SANTOS; REAL, CAROLINE CRISTIANO; UZUELI, DANIEL HENRIQUE; SA, ULISSES LACERDA DE FIGUEIREDO; MARQUES, FABIO LUIZ NAVARRO; COLNAGO, LUIZ ALBERTO; ESPOSITO, BRENO PANNIA. Development of a platform for the production of multiple modal chelating and imaging agents using desferrioxamine and bovine albumin as a model. CHEMICAL PAPERS, v. 75, n. 3, p. 1157-1163, MAR 2021. (16/03709-9, 17/16379-0)

DA SILVA, GABRIEL SOUTO; SHANG, ZHUO; KALANSURIYA, PABASARA; CAPON, ROBERT J.; ESPOSITO, BRENO PANNIA. Antioxidant activity and cellular uptake of the hydroxamate-based fungal iron chelators pyridoxatin, desferriastechrome and desferricoprogen. BIOMETALS, v. 32, n. 4, p. 707-715, AUG 2019. (16/03709-9)

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, v. 34, n. 2, JAN 2021. (15/14360-4, 18/19684-0, 16/03709-9)

ARNDT, ANDERSON; LIRIA, CLEBER WANDERLEI; YOKOYAMA-YASUNAKA, JENICER K. U.; TERESA MACHINI, M.; BORTOLIN UHANA, SILVIA RENI; ESPOSITO, BRENO PANNIA. New iminodibenzyl derivatives with anti-leishmanial activity. Journal of Inorganic Biochemistry, v. 172, p. 9-15, JUL 2017. (16/03709-9, 11/50318-1)

ALVARADO HUAYHUAZ, JESUS ANTONIO; VITORINO, HECTOR AGUILAR; CAMPOS, OTHON SOUTO; PIRES SERRANO, SILVIA HELENA; KANEKO, TELMA MARY; ESPOSITO, BRENO PANNIA. Desferrioxamine and desferrioxamine-caffeine as carriers of aluminum and gallium to microbes via the Trojan Horse Effect. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, v. 41, p. 16-22, 2017. (16/03709-9, 11/50318-1)