2026-04-17T01:49:03Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/692792025-12-04T21:45:08Zcom_2072_1057col_2072_478917col_2072_478933

urn:hdl:2445/69279 A photoactivatable PtIV anticancer complex conjugated to the RNA ligand guanidinoneomycin Shaili, Evyenia Fernández-Giménez, Marta Rodríguez-Astor, Savina Gandioso, Albert Sandín, Lluís García-Vélez, Carlos Massaguer i Vall-llovera, Anna Clarkson, Guy J. Woods, Julie A. Sadler, Peter Marchán Sancho, Vicente Medicaments antineoplàstics ADN Fotoquímica Platí Relacions estructura-activitat (Bioquímica) Quimioteràpia del càncer Antineoplastic agents DNA Photochemistry Platinum Structure-activity relationships (Biochemistry) Cancer chemotherapy A photoactivatable platinum(IV) complex, trans,trans,trans-[Pt(N3)2(OH)(succ)(py)2] (succ=succinylate, py=pyridine), has been conjugated to guanidinoneomycin to study the effect of this guanidinum-rich compound on the photoactivation, intracellular accumulation and phototoxicity of the pro-drug. Surprisingly, trifluoroacetic acid treatment causes the replacement of an azido ligand and the axial hydroxide ligand by trifluoroacetate, as shown by NMR spectroscopy, MS and X-ray crystallography. Photoactivation of the platinum-guanidinoneomycin conjugate in the presence of 5′-guanosine monophosphate (5′-GMP) led to the formation of trans-[Pt(N3)(py)2(5′-GMP)]+, as does the parent platinum(IV) complex. Binding of the platinum(II) photoproduct {PtN3(py)2}+ to guanine nucleobases in a short single-stranded oligonucleotide was also observed. Finally, cellular uptake studies showed that guanidinoneomycin conjugation improved the intracellular accumulation of the platinum(IV) pro-drug in two cancer cell lines, particularly in SK-MEL-28 cells. Notably, the higher phototoxicity of the conjugate in SK-MEL-28 cells than in DU-145 cells suggests a degree of selectivity towards the malignant melanoma cell line. 2016-02-05T11:48:53Z 2016-11-02T23:01:15Z 2015-11-02 2016-02-05T11:48:53Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Versió postprint del document publicat a: http://dx.doi.org/10.1002/chem.201502373 Chemistry-A European Journal, 2015, vol. 21, num. 50, p. 18474-18486 http://dx.doi.org/10.1002/chem.201502373 (c) Wiley-VCH, 2015 info:eu-repo/semantics/openAccess Wiley-VCH Articles publicats en revistes (Química Inorgànica i Orgànica)