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Título:	Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes
Autor/a:	Barragán, Flavia; Carrión-Salip, Dolors; Gómez-Pinto, Irene; González-Canto, Alejandro; Sadler, Peter; Llorens, Rafael de; Moreno Martínez, Virtudes; González, Carlos; Massaguer i Vall-llovera, Anna; Marchán Sancho, Vicente
Otros autores:	Universitat de Barcelona
Abstract:	Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η6-bip)Os(4-CO2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η6-p-cym)RuCl(dap)]+ (p-cym = p-cymene) (5), and [(η6-p-cym)RuCl(imidazole-CO2H)(PPh3)]+ (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC50 = 63 ± 2 μM in MCF-7 cells and IC50 = 26 ± 3 μM in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC50 = 45 ± 2.6 μM in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically.
Materia(s):	-Cèl·lules canceroses -Càncer -Quimioteràpia del càncer -Pèptids -Receptors cel·lulars -Cancer cells -Cancer -Cancer chemotherapy -Peptides -Cell receptors
Derechos:	(c) American Chemical Society , 2012
Tipo de documento:	Artículo Artículo - Versión aceptada
Editor:	American Chemical Society
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