Barragán, FlaviaCarrión-Salip, DolorsGómez-Pinto, IreneGonzález-Cantó, AlejandroSadler, PeterLlorens Duran, Rafael deMoreno Martínez, VirtudesGonzález, CarlosMassaguer i Vall-llovera, AnnaMarchán Sancho, Vicente2013-06-072013-12-3120121043-1802https://hdl.handle.net/2445/44121Conjugates 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.56 p.application/pdfeng(c) American Chemical Society , 2012Cèl·lules cancerosesCàncerQuimioteràpia del càncerPèptidsReceptors cel·lularsCancer cellsCancerCancer chemotherapyPeptidesCell receptorsinfo:eu-repo/semantics/article6176362013-06-07info:eu-repo/semantics/openAccess