Repozytorium

Solution structure, oxidative DNA damage, biological activity and molecular docking of ternary copper(II) L−argininato complexes

Autorzy

Agnieszka Wojciechowska

Romualda Bregier-Jarzębowska

Urszula K. Komarnicka

Agnieszka Szuster-Ciesielska

Michał Sułek

Agnieszka Bojarska-Junak

Ramadan M. Ramadan

Julia Jezierska

Rok wydania

2025

Czasopismo

Biochimie

Numer woluminu

230

Strony

121-137

DOI

10.1016/j.biochi.2024.11.009

Kolekcja

Naukowa

Język

Angielski

Typ publikacji

Artykuł

Streszczenie

Continuing our search for metal drugs with markedly higher toxicity to cancer cells than to normal cells, we evaluated the effect of 2,2′-bipyridine (bpy) as a co-ligand in the compounds [Cu(μ−O,O’−NO3)(L−Arg)(bpy)]NO3}n (1) and [CuCl(L−Arg)(bpy)]Cl·3H2O (2) (L−Arg = L−arginine), on DNA interaction, cytotoxic and antiproliferative activity, compared to the effects induced by other co-ligands i.e. 1,10-phenanthroline (phen) and SCN− ions, in similar Cu(II) compounds we have studied previously. Potentiometric, X-band EPR and UV–Vis experiments were first used to structurally characterise the complexes formed in solutions 1 and 2 and in model Cu(II)/bpy/L−Arg systems. Gel electrophoresis in the presence of H2O2 was used to identify DNA damage by 1 and 2. In addition, cyclic voltammetry of both compounds was performed to confirm the existence of Cu(II)/Cu(I) redox pairs involved in the free radical mechanism of this DNA damage. The DNA binding constants of 1 and 2 were determined spectrophotometrically. The selectivity of the cytotoxic and antiproliferative activity of compounds 1 and 2 was tested in vitro against human lung adenocarcinoma (A549), liver cancer (HepG2) and normal cells in comparison with those previously observed by us for compounds consisting of phen and SCN− ligands. Molecular docking calculations were performed for [Cu(L−Arg)(bpy)]2+ species (arraised in solutions of 1 and 2) interacting with B-DNA (aureolin), metalloproteinase (S. aureus) and penicillin-binding protein (E. coli) to determine the nature of the complex-receptor interaction, potential binding modes and energies.

Słowa kluczowe

L−Arginine, Cu(II) complexes, Potentiometric study, UV–Vis and EPR spectroscopies, Free radicals, Cytotoxic and antiproliferative potential, Molecular docking

Adres publiczny

http://dx.doi.org/10.1016/j.biochi.2024.11.009

Strona internetowa wydawcy

http://www.elsevier.com

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