2026-04-17T02:55:31Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Shaili, Evyenia author Fernández-Giménez, Marta author Rodríguez-Astor, Savina author Gandioso, Albert author Sandín, Lluís author García-Vélez, Carlos author Massaguer i Vall-llovera, Anna author Clarkson, Guy J. author Woods, Julie A. author Sadler, Peter author Marchán Sancho, Vicente author 2016-02-05T11:48:53Z 2016-11-02T23:01:15Z 2015-11-02 2016-02-05T11:48:53Z 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. 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 PtIV anticancer complex conjugated to the RNA ligand guanidinoneomycin