Cytotoxic and Antimicrobial Properties of Copper(II) Complexes of Pyridine and Benzimidazole Derivatives

Abstract

The cytotoxic and antimicrobial activity of a series of six copper(II) complexes with phosphate and hydroxymethyl derivatives of pyridine and benzimidazole were investigated. The complexes and the corresponding free ligands were tested against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922, Proteus hauseri ATCC 13315, and Candida albicans ATCC 10231. Among the tested copper(II) complexes, compounds 2 and 5 containing 1H‐benzimidazol‐2‐ylmethyl diethyl phosphate and 2‐(hydroxymethyl)benzimidazole as ligands, respectively, were most active and limited the growth of S. aureus, E. coli, and C. albicans by 30–60 % according to concentration and microorganism. The in vitro cytotoxic activity of the CuII complexes and free ligands towards cancerous B16 (murine melanoma) and non‐cancerous 10T1/2 (murine fibroblasts) cell lines was determined. The 10T1/2 cells were treated with the compounds at concentrations equal to IC50 values for B16 cells. In spite of the use of relatively high concentrations of the complexes, the viability of 10T1/2 cells was very high, ca. 80 % in some cases. Stability of the CuII complexes was evaluated in water solutions by UV/Vis spectroscopy. The copper(II) complex of 4‐(hydroxymethyl)pyridine was synthesized and identified.

Copper(II) Complexes with Mixed Heterocycle Ligands as Promising Antibacterial and Antitumor Species

“…It is worth mentioning that for other copper compounds tested on melanoma cells the reported IC 50 values were similar [ 39 , 40 , 41 ] or even higher [ 42 ] compared with the values found for complexes ( 1 ) and ( 2 ).…”

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands

“…For B16 cells, when treated with (2), the cell viability decreased to 5%, with IC 50 values of 6.88 µg/mL (7.6 µM) after 24 h treatment and 4.15 µg/mL (4.58 µM) after 48 h, respectively (Table 3). The ligand dmtp did not affect the viability of either BJ or B16 cells at 24 or 48 h. It is worth mentioning that for other copper compounds tested on melanoma cells, the reported IC 50 values were similar [35][36][37][38][39][40][41][42][43], and only one study reported lower values [38] compared with those found for complex (1).…”

“…The Cu(II) systems represent beneficial species from this point of view, considering their reduced systemic toxicity [16]. Thus, several Cu(II) complexes were studied and proved to be as effective for melanoma treatment [18,29,[35][36][37][38][39][40][41][42][43]-some having, in addition, low toxicity on normal cells [18,29,[39][40][41][42][43].…”

“…Yield: 78% (0.34 g). Analysis, found: C, 42 [Cu(phen)(dmtp) 2 (OH 2 )](ClO 4 ) 2 •dmtp (2): To a solution, containing copper(II) perchlorate hexahydrate (0.186 g, 0.5 mmol) in 50 mL water, a solution containing phen (0.090 g, 1 mmol) in 25 mL ethanol was added. This mixture was magnetically stirred at 50 • C for 2 h, until the color turned green, and then a solution containing dmtp (0.222 g, 1.5 mmol) in 25 mL ethanol was added.…”

Tailoring copper(ii) complexes with pyridine-4,5-dicarboxylate esters for anti-Candida activity

“…15 On the other hand, copper(II) complexes with the phosphate and hydroxymethyl derivatives of pyridine and benzimidazole did not inhibit completely the growth of the studied bacteria and fungi up to 200 µg mL −1 . 16 In the present study, pyridine-4,5-dicarboxylate esters, namely dimethyl 2-(thiazol-2-yl)pyridine-4,5-dicarboxylate ( py-2tz), dimethyl 2-(4-methylthiazol-2-yl)pyridine-4,5-dicarboxylate ( py-2metz) and dimethyl 2,2′-bipyridine-4,5-dicarboxylate ( py-2py) (Scheme 1), were used as ligands for the synthesis of copper(II) complexes. These ligands have been previously used for the synthesis of silver(I) complexes as efficient agents for the control of cow mastitis associated pathogens 17 and of ruthenium(II) complexes as inhibitors of aldo-keto reductases (AKRs) 18 and 15-lipoxygenase-1.…”