Article In: orcid, cienciavitae

Synthesis, characterization and biological evaluation of In(iii) complexes anchored by DOTA-like chelators bearing a quinazoline moiety

Metallomics

Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros; Raquel Garcia; Eva Toth — 2010 — The Royal Society of Chemistry

Key information

Authors:

Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Raquel Garcia; Vojtech Kubícek; Bohuslav Drahos; Maria de Lurdes Barrela Patricio Gano (Maria de Lurdes Barrela Patrício Gano); Isabel Santos (Isabel da Graça Rego dos Santos); Antonio Paulo (António Manuel Rocha Paulo); Isabel Cordeiro dos Santos (Isabel Maria Fernandes Cordeiro dos Santos); Eva Toth

Published in

06/17/2010

Abstract

Following previous studies with a DOTA-like bifunctional chelator (H3L1) containing an ethylenic linker between the macrocycle backbone and a quinazoline pharmacophore, we synthesized and fully characterized a congener macrocyclic ligand (H3L2) having a longer, five-carbon spacer for the linkage of the quinazoline moiety. Both H3L1 and H3L2 were used to prepare indium(III) complexes aiming at their evaluation as radioactive probes for in vivo targeting of EGFR-TK. The protonation constants (log KHi) of H3L2 were determined by potentiometry and UV-Vis spectrophotometry and the values found are 12.18, 9.74, 4.99, 3.91 and 2.53. The stability and protonation constants of InL (L = L1, L2) were also obtained from a combined potentiometry and UV-VIS spectrophotometry study. The reaction of InCl3 with H3L1 and H3L2 led to the formation of the well-defined complexes InL1 and InL2, containing In(III) ions coordinated by a seven (N4,O3) donor atom set. These new complexes were fully characterized by spectroscopic methods (IR, NMR, ESI-MS), HPLC and by X-ray diffraction analysis in the case of InL1. The radioactive congener 111InL2 was prepared from the reaction of 111In–chloride with H3L2, in high yield and high radiochemical purity. 111InL2 is a neutral complex that presents a hydrophilic character and exhibits a high in vitro and in vivo stability. H3L2 and InL2 do not inhibit the cell growth of A431 cervical carcinoma cells. In this EGFR-expressing cell line, 111InL2 has shown very low cell internalization. These findings indicate that these DOTA-like chelators are not the best suited bifunctional ligands to obtain In(III) complexes with adequate biological properties for targeting the EGFR-TK

Publication details

Authors in the community:

Publication version

AO - Author's Original

Publisher

The Royal Society of Chemistry

Title of the publication container

Metallomics

First page or article number

571

Last page

580

Volume

2

Issue

8

DOI

10.1039/c004797j

Fields of Science and Technology (FOS)

health-sciences - Health sciences

Keywords

  • DOTA-like chelators
  • In(III) complexes
  • EGFR-expressing cell line
  • Potentiometric and UV-Vis studies

Publication language (ISO code)

eng - English

Alternative identifier (URI)

http://www.scopus.com/inward/record.url?eid=2-s2.0-77955358453&partnerID=MN8TOARS

Rights type:

Only metadata available

Financing entity

Isabel Cordeiro dos Santos