Probing the DNA Reactivity and the Anticancer Properties of a Novel Tubercidin-Pt(II) Complex

Abstract

<jats:p>Herein, we reported on the synthesis of a novel Pt(II) neutral complex having as ligand the nucleoside tubercidin, a potent anti-tumor agent extracted from the bacterium Streptomyces Tubercidicus. In detail, the chelation of the metal by a diamine linker installed at C6 purine position of tubercidin assured the introduction of a cisplatin-like unit in the molecular scaffold. The behavior of the synthesized complex with a double-strand DNA model was monitored by CD spectroscopy and compared with that of cisplatin and tubercidin. In addition, the cell viability was evaluated against HeLa, A375 and WM266 human cancer cell lines using the MTT test. Lastly, the results of the apoptotic assay (FITC Annexin V) performed on the HeLa cancer cell line are also reported.</jats:p>

Platinum-Nucleos(t)ide Compounds as Possible Antimetabolites for Antitumor/Antiviral Therapy: Properties and Perspectives

“…D’Errico et al tested the anticancer potential of some neutral platinum(II) complexes carrying the cisplatin-like moiety linked to tubercidin through a N -alkyl-amide diamino spacer at the purine C6 position. Thanks to their capability to react more quickly than cisplatin with model duplex DNA chains, it would be interesting to also evaluate the antiviral activity of such complexes [ 101 , 102 , 103 , 104 , 105 ].…”

“…Nevertheless, since the discovery of the antitumor activity of platinum compounds, these molecules were studied worldwide in order to improve their efficacy and selectivity. Considering that most of the currently approved antiviral drugs are based on nucleos(t)ide analogues, the study of the ligand properties of modified nucleos(t)ides towards metal centers is an interesting promising field in the design of novel antivirals [ 102 , 121 ]. DNA is a primary target for many antiviral drugs because inhibition of DNA and/or RNA synthesis during viral replication is an important step, sometimes necessary, for the design of new antiviral drugs.…”

Synthesis, Antiproliferative Activity, and DNA Binding Studies of Nucleoamino Acid-Containing Pt(II) Complexes

“…After 24 h, cells were treated for 48 h with the compounds previously solubilized. In detail, the Pt complexes and DAP(T)–OH were dissolved in DMSO at a 10 mM concentration, while cisplatin was solubilized in an aqueous solution of DMSO (10%)/NaCl (0.9%), at a 2 mM concentration [ 50 ], then diluted with growth medium until the final solution contained no more than 0.5% DMSO, well-tolerated by in vitro cell cultures. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT, Sigma Aldrich, Milano, Italy) after 48 h incubation [ 51 ].…”

“…For all the experiments, oligonucleotides were dissolved at 2 μM concentration, stock solutions of ligands [ T1 , T2 , and DAP(T)–OH] were prepared at 7 mM conc. in DMSO, whereas stock CDDP solution was obtained at a 7 mM concentration in an aqueous solution of DMSO (10%)/NaCl (0.9%) [ 50 ]. A buffer solution of 7 mM Na 2 HPO 4 /NaH 2 PO 4 , 100 mM KCl (pH 7.2) was used for the studies on the interaction between the DNA model systems and the platinum-based complexes.…”

Synthesis and anticancer activities of novel Pt (II) and Pd (II) complexes with 4‐(2,2′:6′,2″‐terpyridin‐4′‐yl)phenol as ligand

“…1 was more potent than 2; both 1 and 2 induced an apoptosis rate higher than that of either Pt or Pd. [45][46][47] Morphological observation of HeLa cells was performed by DAPI staining fluorescence microscopy, and photographs were obtained at 20Â and 40Â magnification. HeLa cells were treated with complexes 1 and 2 and with the absence of complexes for 24 h, as shown in Figures 5 and S8.…”