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Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents

Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor...

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Autores principales: Makrypidi, Konstantina, Kiritsis, Christos, Roupa, Ioanna, Triantopoulou, Sotiria, Shegani, Antonio, Paravatou-Petsotas, Maria, Chiotellis, Aristeidis, Pelecanou, Maria, Papadopoulos, Minas, Pirmettis, Ioannis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960821/
https://www.ncbi.nlm.nih.gov/pubmed/36838773
http://dx.doi.org/10.3390/molecules28041786
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author Makrypidi, Konstantina
Kiritsis, Christos
Roupa, Ioanna
Triantopoulou, Sotiria
Shegani, Antonio
Paravatou-Petsotas, Maria
Chiotellis, Aristeidis
Pelecanou, Maria
Papadopoulos, Minas
Pirmettis, Ioannis
author_facet Makrypidi, Konstantina
Kiritsis, Christos
Roupa, Ioanna
Triantopoulou, Sotiria
Shegani, Antonio
Paravatou-Petsotas, Maria
Chiotellis, Aristeidis
Pelecanou, Maria
Papadopoulos, Minas
Pirmettis, Ioannis
author_sort Makrypidi, Konstantina
collection PubMed
description Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)(5) and fac-[NEt(4)](2)[ReBr(3)(CO)(3)] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)(3)] (5a) and fac-[Re(SNO)(CO)(3)] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[(99m)Tc(CO)(3)](+) core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[(99m)Tc][Tc(OH(2))(3)(CO)(3)](+) precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC(50) = 8.85 ± 2.62 μM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC(50) value of 26.11 nM. Biodistribution studies of the (99m)Tc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system.
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spelling pubmed-99608212023-02-26 Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents Makrypidi, Konstantina Kiritsis, Christos Roupa, Ioanna Triantopoulou, Sotiria Shegani, Antonio Paravatou-Petsotas, Maria Chiotellis, Aristeidis Pelecanou, Maria Papadopoulos, Minas Pirmettis, Ioannis Molecules Article Τhe Epidermal Growth Factor Receptor tyrosine kinase inhibitor (EGFR-TKI) 6-amino-4-[(3-bromophenyl) amino]quinazoline was derivatized with 6-bromohexanoyl-chloride and coupled with the tridentate chelating agents N-(2-pyridylmethyl) aminoethyl acetic acid (PAMA) and L(+)-cysteine bearing the donor atom set NNO and SNO, respectively. The rhenium precursors ReBr(CO)(5) and fac-[NEt(4)](2)[ReBr(3)(CO)(3)] were used for the preparation of the Re complexes fac-[Re(NNO)(CO)(3)] (5a) and fac-[Re(SNO)(CO)(3)] (7a) which were characterized by NMR and IR spectroscopies. Subsequently, the new potential EGFR inhibitors were labeled with the fac-[(99m)Tc(CO)(3)](+) core in high yield and radiochemical purity (>90%) by ligand exchange reaction using the fac-[(99m)Tc][Tc(OH(2))(3)(CO)(3)](+) precursor. The radiolabeled complexes were characterized by comparative HPLC analysis with the analogous rhenium (Re) complexes as references. In vitro studies in the A431 cell lines showed that both ligands and Re complexes inhibit A431 cell growth. Complex 5a demonstrated the highest potency (IC(50) = 8.85 ± 2.62 μM) and was further assessed for its capacity to inhibit EGFR autophosphorylation, presenting an IC(50) value of 26.11 nM. Biodistribution studies of the (99m)Tc complexes in healthy mice showed high in vivo stability for both complexes and fast blood and soft tissue clearance with excretion occurring via the hepatobiliary system. MDPI 2023-02-14 /pmc/articles/PMC9960821/ /pubmed/36838773 http://dx.doi.org/10.3390/molecules28041786 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Makrypidi, Konstantina
Kiritsis, Christos
Roupa, Ioanna
Triantopoulou, Sotiria
Shegani, Antonio
Paravatou-Petsotas, Maria
Chiotellis, Aristeidis
Pelecanou, Maria
Papadopoulos, Minas
Pirmettis, Ioannis
Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents
title Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents
title_full Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents
title_fullStr Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents
title_full_unstemmed Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents
title_short Evaluation of Rhenium and Technetium-99m Complexes Bearing Quinazoline Derivatives as Potential EGFR Agents
title_sort evaluation of rhenium and technetium-99m complexes bearing quinazoline derivatives as potential egfr agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960821/
https://www.ncbi.nlm.nih.gov/pubmed/36838773
http://dx.doi.org/10.3390/molecules28041786
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