A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays

M. Amélia Santos, Sofia Gama, Lurdes Gano, Guilhermina Cantinho, E. Farkas

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3′-aminopropyl)-3-hydroxy2-methyl-4-pyridinone)), IDAPr(3,4-HP)2, has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (log D = -1.72). In vivo assays showed much more rapid clearance of 67Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.

Original languageEnglish
Pages (from-to)3772-3781
Number of pages10
JournalDalton Transactions
Issue number21
DOIs
Publication statusPublished - Nov 7 2004

Fingerprint

Pyridones
Chelating Agents
Complexation
Metal ions
Assays
Metals
Derivatives
Radioactivity
Chelation
Zinc
Tissue
Ligands
Pharmaceutical Preparations
hard metal

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays. / Santos, M. Amélia; Gama, Sofia; Gano, Lurdes; Cantinho, Guilhermina; Farkas, E.

In: Dalton Transactions, No. 21, 07.11.2004, p. 3772-3781.

Research output: Contribution to journalArticle

@article{36f0c394c76f41728812e27313fe68f7,
title = "A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays",
abstract = "A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3′-aminopropyl)-3-hydroxy2-methyl-4-pyridinone)), IDAPr(3,4-HP)2, has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (log D = -1.72). In vivo assays showed much more rapid clearance of 67Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.",
author = "Santos, {M. Am{\'e}lia} and Sofia Gama and Lurdes Gano and Guilhermina Cantinho and E. Farkas",
year = "2004",
month = "11",
day = "7",
doi = "10.1039/b409357g",
language = "English",
pages = "3772--3781",
journal = "Dalton Transactions",
issn = "1477-9226",
publisher = "Royal Society of Chemistry",
number = "21",

}

TY - JOUR

T1 - A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays

AU - Santos, M. Amélia

AU - Gama, Sofia

AU - Gano, Lurdes

AU - Cantinho, Guilhermina

AU - Farkas, E.

PY - 2004/11/7

Y1 - 2004/11/7

N2 - A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3′-aminopropyl)-3-hydroxy2-methyl-4-pyridinone)), IDAPr(3,4-HP)2, has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (log D = -1.72). In vivo assays showed much more rapid clearance of 67Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.

AB - A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3′-aminopropyl)-3-hydroxy2-methyl-4-pyridinone)), IDAPr(3,4-HP)2, has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (log D = -1.72). In vivo assays showed much more rapid clearance of 67Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.

UR - http://www.scopus.com/inward/record.url?scp=9644260383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9644260383&partnerID=8YFLogxK

U2 - 10.1039/b409357g

DO - 10.1039/b409357g

M3 - Article

SP - 3772

EP - 3781

JO - Dalton Transactions

JF - Dalton Transactions

SN - 1477-9226

IS - 21

ER -