The first copper (II) complex with 1,10-phenanthroline and Salubrinal with interesting biochemical properties

Sebastiano Masuri

First

;enzo cadoni

Second

;Maria Grazia Cabiddu;Francesco Isaia;Maria Giovanna Demuru;Lukáš Moráň;David Bucek;Petr Vanhara;josef havel

Penultimate

;Tiziana Pivetta

Last

2020-01-01

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Abstract

The novel copper complex [Cu(phen)2(salubrinal)](ClO4)2 (C0SAL) has been synthesised and characterised. Copper(II) is coordinated by salubrinal through the thionic group, as shown by the UV-Vis, IR, ESI-MS and tandem mass results, together with the theoretical calculations. The formed complex shown a DPPH radical scavenging ability higher than that of the salubrinal alone. Studies on the lipid oxidation inhibition, shown that the C0SAL concentration, required to inhibit the enzyme, was lower than that of salubrinal. The inhibition of the enzyme could take place via allosteric modulation, as suggested by docking calculations. C0SAL shown a good cytotoxic activity on A2780 cells, 82 fold higher than the precursor salubrinal and 1.4 fold higher than [Cu(phen)2(H2O)](ClO4)2. Treatment with C0SAL in SKOV3 ovarian cancer cells induced expression of GRP-78 and DDIT3 regulators of ER-stress response. The cytotoxic effect of C0SAL was reverted in the presence of TUDCA, suggesting that C0SAL induces the cell death by ER-stress. In A2780 cells treated with C0SAL γ-H2AX was accumulated, suggesting that also DNA was involved.