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Potential bio-protective effect of copper compounds: mimicking SOD and peroxidases enzymes and inhibiting acid phosphatase as a target for anti-osteoporotic chemotherapeutics

  • Nancy Martini
  • Juliana E. Parente
  • Franco D´Alessandro
  • Marilin Rey
  • Alberto Rizzi
  • Patricia A. M. Williams
  • Evelina G. Ferrer
Original Article
  • 44 Downloads

Abstract

Copper complexes with transformed methimazole ligand have been synthesized and characterized by elemental analysis, conductivity measurements, thermogravimetric analysis, EPR, FTIR and UV–Vis spectroscopies. Results support their stoichiometries and geometrical structures: [Cu(C4H5N2S)2Cl2]·2H2O(1), [Cu(C8H10N4S)SO4H2O](2) and [Cu(C8H10N4S)SO4](3). ((C4H5N2)2S: bis(l-methylimidazol-2-yl)sulfide; (C4H5N2S)2 = Bis[bis(l-methylimidazol-2-yl)disulfide]) Concurrently, the structurally distinct soluble species corresponding to complexes (1) and (2) were subsequently used in an in vitro investigation of their potential biological properties. In view of their possible pharmaceutical activity, the complexes were in vitro evaluated as phosphatase acid inhibitors. Their radical bio-protective effects were also studied measuring the effect against DPPH and O2•− radicals. Additional catalytic properties as peroxidase mimics were evaluated using Michaelis–Menten kinetic model by means of phenol red and pyrogallol assays. The complexes exhibited catalytic bromination activity and the ability to oxidize pyrogallol substrate indicating that they can be considered as functional models. The relationships between the structures and the in vitro biological activities have also been considered. Serum protein albumin has attracted the greatest interest as drug carrier and the affinity of biological/pharmaceutical compound is relevant to the development of new medicine. In that sense, interaction studies by fluorescence and EPR spectroscopies were performed showing the binding capacity of the complexes.

Keywords

Copper complexes Phosphatase inhibition Peroxidase-like activity Superoxide dismutase activity 

Abbreviations

[Cu(C4H5N2S)2Cl2]·2H2O

Complex(1)

[Cu(C8H10N4S)SO4H2O]

Complex(2)

[Cu(C8H10N4S)SO4]

Complex(3)

ABTS

2,2′-Azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt

AcP

Acid phosphatase

BSA

Bovine serum albumin

DMF

Dimethylformamide

DMSO

Dimethyl sulfoxide

FCS

Fetal calf serum

HEPES

Buffered saline, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

NADH

Reduced nicotinamide adenine dinucleotide

NBT

Nitroblue tetrazolium

NTA

Nitrilotriacetic acid

PMS

Phenazine methosulfate

p-NPP

Paranitrophenyl phosphate

Tris–HCl

Tris(hydroxymethyl)aminomethane hydrochloride

Notes

Acknowledgements

This work was supported by CONICET (PIP 0611, PIP 0550), ANPCyT (PICT16-1814, PICT14-1742, PICT17-2186), UNLP (X777), UNL (CAI+D 2016-50420150100070LI) of Argentina. LGN and EGF are Research Fellows of CONICET. JEP and PAMW are Research Fellows of CICPBA, Argentina.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11033_2018_4542_MOESM1_ESM.docx (5 mb)
Supplementary material 1 (DOCX 5085 KB)

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Nancy Martini
    • 1
  • Juliana E. Parente
    • 1
  • Franco D´Alessandro
    • 1
  • Marilin Rey
    • 2
  • Alberto Rizzi
    • 2
  • Patricia A. M. Williams
    • 1
  • Evelina G. Ferrer
    • 1
  1. 1.CEQUINOR, CONICET-CICPBA-UNLP, Faculty of Exact SciencesNational University of La PlataLa PlataArgentina
  2. 2.Physics Department, Faculty of Biochemistry and Biological SciencesNational University of the LitoralSanta FeArgentina

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