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

17/06/2010

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

Autores da comunidade :

• 

  M

  Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros

  ist25375

  Afiliações e fontes

  De: orcid

  ID: 10910727

  De: cienciavitae

  ID: 616709

• 

  M

  Maria de Lurdes Barrela Patrício Gano

  ist25373

  Afiliações e fontes

  De: cienciavitae

  ID: 1330005

• 

  I

  Isabel da Graça Rego dos Santos

  ist25348

• 

  A

  António Manuel Rocha Paulo

  ist126677

  Afiliações e fontes

  De: orcid

  ID: 10942926

  De: cienciavitae

  ID: 614553

• 

  I

  Isabel Maria Fernandes Cordeiro dos Santos

  ist171926

  Afiliações e fontes

  De: orcid

  ID: 10933928

AO - Versão original do autor

The Royal Society of Chemistry

Metallomics

571

580

2

8

10.1039/c004797j

health-sciences - Ciências de Saúde

Palavras-chave

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

eng - Inglês

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

Entidade financiadora da bolsa/projeto

Isabel Cordeiro dos Santos