Synthesis, structure and molecular modeling of a ZnII-Phenolate complex as a model for ZnII-Containing tyrosinate metalloenzymes

Lanznaster, Maurício; Neves, Ademir; Vencato, Ivo; Bortoluzzi, Adaı́lton J.; Gallardo, Hugo; Machado, Sérgio P.; Moreno, Aline; Assumpção, Chagas

doi:10.1590/s0103-50532006000200011

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…The metal centers also dictate the preferential cis or trans orientation of equivalent phenolates and other donor sets in vicinal ligands, with 3d 5 highspin ions displaying a cis arrangement and 3d 6 lowspin and 3d 7 highspin ions , supporting a trans orientation. Species 1 reinforces the notion of an alltrans mode for 3d 8 configurations, whereas 2 seems to fall within other 3d 10 configurations ,− lacking a clear preference. Another remark is that, while most of the O phenolate bond lengths for 1 and 2 are comparable at 2.02−2.05 Å, one of the Zn−O phenolate bonds for 2 is elongated, reaching ca.…”

Section: Resultssupporting

confidence: 73%

Comparative Activities of Nickel(II) and Zinc(II) Complexes of Asymmetric [NN′O] Ligands as 26S Proteasome Inhibitors

et al. 2009

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In this study, we compare the proteasome inhibition capabilities of two anticancer candidates, [Ni(LIA)2] (1) and [Zn(LIA)2] (2), where LIA- is the deprotonated form of the ligand 2,4-diiodo-6-(((2-pyridinylmethyl)amino)methyl)phenol. Species 1 contains nickel(II), a considerably inert ion that favors covalency, whereas 2 contains zinc(II), a labile transition metal ion that favors predominantly ionic bonds. We report on the synthesis and characterization of 1 and 2 using various spectroscopic, spectrometric, and structural methods. Furthermore, the pharmacological effects of 1 and 2, along with the salts NiCl2 and ZnCl2, were evaluated in vitro and in cultured human cancer cells in terms of their proteasome-inhibitory and apoptotic cell death-inducing capabilities. It is shown that neither NiCl2 nor 1 have the ability to inhibit the proteasome activity at any sustained levels. However, ZnCl2 and 2 showed superior inhibitory activity to the chymotrypsin-like activity of both 26S proteasome (IC50 = 5.7 and 4.4 μmol/L, respectively) and purified 20S proteasome (IC50 = 16.6 and 11.7 μmol/L, respectively) under cell-free conditions. Additionally, inhibition of proteasomal activity in cultured prostate cancer cells by 2 was associated with higher levels of ubiquitinated proteins and apoptosis. Treatment with either the metal complex or the salt was relatively non-toxic toward human normal cells. These results strengthen the current working hypothesis that fast ligand dissociation is required to generate an [MLIA]+ pharmacophore, capable of interaction with the proteasome. This interaction, possibly via N-terminal threonine aminoacids present in the active sites, renders the proteasome inactive. Our results present a compelling rationale for 2, along with its gallium(III) and copper(II) congeners to be further investigated as potential anticancer drugs that act as proteasome inhibitiors.

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Section: Resultssupporting

confidence: 73%

Comparative Activities of Nickel(II) and Zinc(II) Complexes of Asymmetric [NN′O] Ligands as 26S Proteasome Inhibitors

et al. 2009

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“…The axial Zn-O benzoate bond (1.95 Å), on the other hand, is nearly equivalent to the equatorial Zn-O phenolate bond (1.96 Å) in 9. Equally relevant is the precise crystallographic work described by Neves et al [31][32][33] on zinc-phenolate ligands. It has been postulated that both the nature of the phenol ring substituent and the geometry adopted around the metal play a crucial role in the length of the Zn-O phenolate bond.…”

Section: Molecular Structures and Coordination Modesmentioning

confidence: 99%

On the Effect of Coordination and Protonation Preferences in the Amphiphilic Behavior of Metallosurfactants with Asymmetric Headgroups

et al. 2009

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(9) were synthesized to model the stoichiometric, coordination, and protonation chemistry in the waxy metallosurfactants 1-4. Detailed data analysis and comparison between 1-4 and 5-9 involved mass spectrometric and spectroscopic methods along with crystallographic determination of 5 (P2 1 /c), 6 (P1), 7 (P2 1 /c), 8Ј (the analogue of 8 with tetraphenylborate counterions, P2 1 /c), and 9 (P1). DFT calculations were used to identify the frontier orbitals, polarizability, and dipole moments. Species 1-4 had their

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Synthesis, characterization and antiglaucoma activity of a novel proton transfer compound and a mixed-ligand Zn(II) complex

Yenikaya

Sari

Bülbül

et al. 2010

Bioorganic & Medicinal Chemistry

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Synthesis, structure and molecular modeling of a ZnII-Phenolate complex as a model for ZnII-Containing tyrosinate metalloenzymes

Cited by 8 publications

References 17 publications

Comparative Activities of Nickel(II) and Zinc(II) Complexes of Asymmetric [NN′O] Ligands as 26S Proteasome Inhibitors

Comparative Activities of Nickel(II) and Zinc(II) Complexes of Asymmetric [NN′O] Ligands as 26S Proteasome Inhibitors

On the Effect of Coordination and Protonation Preferences in the Amphiphilic Behavior of Metallosurfactants with Asymmetric Headgroups

Synthesis, characterization and antiglaucoma activity of a novel proton transfer compound and a mixed-ligand Zn(II) complex

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