Selective cytotoxicity and antifungal properties of copper(II) and cobalt(II) complexes with imidazole-4-acetate anion or 1-allylimidazole

Abstract

The physicochemical properties of metal complexes determine their potential applications as antitumor agents. In this study, the antitumor properties of mononuclear cobalt(II) and copper(II) coordination compounds (stoichiometry: [Co(iaa) 2 (H 2 O) 2 ]·H 2 O (iaa = imidazole-4-acetate anion), [Co(1-allim) 6 ](NO 3 ) 2 (1-allim = 1-allylimidazole), [Cu(iaa) 2 H 2 O] and [Cu(1-allim) 4 (NO 3 ) 2 ]) and their ligands have been evaluated on human lung carcinoma A549 cells and normal bronchial BEAS-2B cells. Designing the chemical structure of new antitumor agents the possible interactions with macromolecules such as DNA or proteins should be take into account. PCR gene tlr4 product served as DNA model, whereas lysozyme and phage-derived endolysin (both peptidoglycan degrading enzymes) were applied as protein/enzyme model. The interactions were analysed using PCR-HRM and circular dichroism, FT-IR, spectrophotometry, respectively. Additionally, the antimicrobial properties of the complexes at a non-cytotoxic concentration were analyzed against S. aureus, E. coli, P. aeruginosa and C. albicans strains. The results obtained in this study showed the selective cytotoxicity of metal complexes, mainly [Cu(1-allim) 4 (NO 3 ) 2 ] towards tumor cells. From all tested compounds, only [Co(iaa) 2 (H 2 O) 2 ] . H 2 O non-covalently interacts with DNA. Cu(II) and Co(II) complexes did not affect the secondary conformation of tested proteins but modified the hydrolytic activity of enzymes (lysozyme and endolysin). Moreover, only [Co(iaa) 2 (H 2 O) 2 ] . H 2 O exhibited the antifungal properties. In conclusion, Co(II) and Cu(II) metal complexes bearing two imidazole-4-acetate ligands seemed to be promising antitumor and antifungal agents for future drug design and application.

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

“…The in vitro tests showed that cobalt(III) complexes (43, Figure 9) were more active against Gram-positive bacteria (e.g., S. aureus) and fungal strains (C. albicans) with MIC values of 0.7-3 and 7-250 µg/mL, respectively, and less active against Gram-negative strains, such as E. coli and K. pneumoniae. Several other types of cobalt metal complexes have been tested for their antimicrobial efficacy, however, their activities were not found remarkably high [111][112][113][114][115][116][117][118][119][120][121].…”

Nontoxic Cobalt(III) Schiff Base Complexes with Broad‐Spectrum Antifungal Activity

“…reported a series of copper(II) and cobalt(II) complexes with the ligands imidazole‐4‐acetate (iaa) and 1‐allylimidazole and found that the Co II ‐iaa compound ( Co2 ) showed a significant decrease (≈5 log) in colony forming units (CFU) against Candida albicans at 60 μM in vitro, while not displaying any cytotoxicity at the same concentration. Unfortunately no dose‐response or activity at lower concentrations were reported [14] . In 2019, Hashmi and co‐workers described the preparation of Co, Ni, Zn, and Cu complexes bearing a 1,10‐phenanthroline ligand as well as a Schiff‐base‐derived ligand with a pendent indole ring (e.g., Ni1 ).…”

“…Unfortunately no dose-response or activity at lower concentrations were reported. [14] In 2019, Hashmi and co-workers described the preparation of Co, Ni, Zn, and Cu complexesb earing a1 ,10-phenanthroline ligand as well as aS chiff-base-de-rived ligand with ap endent indole ring (e.g., Ni1). The cobalt and nickel complexes showed high antifungal activity against aseries of C. albicans strains (includings ome fluconazole-resistant isolates), with MICs ranging from 0.25-8 mgmL À1 .H owever, no studies against other fungal pathogens or cytotoxicity against human cell lines were reported.…”

Antitumor Activity of Pt(II), Ru(III) and Cu(II) Complexes

“…This article presents the main mechanisms of the in vitro anticancer activity of metal complexes (apoptosis, autophagy, cell cycle inhibition, DNA damage) described in the literature to date. Studies on cell lines indicate that metal complexes, especially copper complexes, are selective for cancer cells [ 103 , 104 , 105 ]. Metal complexes might soon prove to be good alternatives to cisplatin, which is still the most popular, but with many side effects and fast emerging drug-resistance in cancer cells.…”