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2012

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/44121

Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes

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http://dx.doi.org/10.1021/bc300173h

Resum

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.

Matèries

Cèl·lules canceroses, Càncer, Quimioteràpia del càncer, Pèptids, Receptors cel·lulars

Matèries (anglès)

Cancer cells, Cancer, Cancer chemotherapy, Peptides, Cell receptors

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Articles publicats en revistes (Química Inorgànica i Orgànica)

Citació

BARRAGÁN, Flavia, CARRIÓN-SALIP, Dolors, GÓMEZ-PINTO, Irene, GONZÁLEZ-CANTÓ, Alejandro, SADLER, Peter, LLORENS DURAN, Rafael de, MORENO MARTÍNEZ, Virtudes, GONZÁLEZ, Carlos, MASSAGUER I VALL-LLOVERA, Anna, MARCHÁN SANCHO, Vicente. Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes. _Bioconjugate Chemistry_. 2012. Vol. 23, núm. 9, pàgs. 1838-1855. [consulta: 20 de gener de 2026]. ISSN: 1043-1802. [Disponible a: https://hdl.handle.net/2445/44121]

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