Insight on Ni(II) and Cu(II) complexes of biguanide derivatives developed as effective antimicrobial and antitumour agents

Abstract

ammonia and formaldehyde and H 2 L 2 : ligand resulted from the condensation of (4) with hydrazine and formaldehyde) were characterized as mononuclear species through information provided by NMR, electronic paramagnetic resonance (EPR) and UV-Vis spectroscopy as well as cyclic voltammetry. All data are consistent with macrocyclic formation by condensation. The complexes adopt a distorted square planar geometry resulting from the chelating behaviour of the corresponding ligands. The EPR spectra recorded after the addition of Cu(II) complexes into the corresponding Ni(II) complexes show a well resolved hyperfine structure with the superhyperfine pattern corresponding to four nitrogen atom donors. The cathodically shift of E pc2 for both series can be correlated with the increased stability of the M(I) species through macrocyclic ligands. Geometry optimization studies for complexes (2), (3), (5) and (6) have further confirmed the experimental data. The pharmacokinetic computational results indicate that the complexes exhibit medium to low intestinal absorption and slow blood-brain barrier permeability but low toxicity. Their predictive pharmacodynamic profiles show that the compounds present the ability to inhibit protease activity. By corroborating the results of the in silico analysis

Biological Properties of Transition Metal Complexes with Metformin and Its Analogues

“…Metformin can be coordinated with a metal center as a part of a macrocycle. For example, macrocyclic Ni complexes 74 and 75 were obtained in two steps via the intermediate formation of a square planar complex 73 with two deprotonated metformin ligands (Scheme 23) [143]. Despite relative structural similarities, 73-75 demonstrated differential selectivity towards various bacterial and fungal strains.…”

“…Overall, 92 demonstrated the strongest inhibitory potential; however, it was not compared with the respective inorganic Cu(II) salt or the clinically used antibiotics [159]. Olar et al prepared mono-and dinuclear tetracoordinate Cu(II) complexes 94-99 (Figure 4) according to the synthetic procedures described earlier [103,104,143,160]. In contrast to structurally similar Ni complexes 73-75, Cu(II) complexes 94-96 were not significantly active against E. faecium, P. aeruginosa and C. albicans and completely devoid of activity against S. aureus, E. coli and C. parapsilosis [143].…”

Metal Complexes—A Promising Approach to Target Biofilm Associated Infections

“…Recent studies indicated that the biguanide incorporation into a macrocycle ligand generated promising complexes [M(dmbgMc)] ( 49 ) (M: Ni, Cu; H 2 dmbgMc: ligand resulted from Hdmbg condensation with ammonia/hydrazine and formaldehyde) for applications in the treatment of infections produced by pathogenic microorganisms, including those complicated by biofilm development. A broad anti-biofilm spectrum on P. aeruginosa , E. faecium , E. faecalis , C. albicans and C. parapsilosis was registered for Ni(II) complex with macrocycle resulted in ammonia system [ 123 ].…”

Copper(II) species with 1‐(o‐tolyl)biguanide: Structural characterization, ROS scavenging, antibacterial activity, biocompatibility and in silico studies

“…[25] Recent studies indicated that the biguanide incorporation into a macrocycle ligand generated promising complexes [CuL] (H 2 L: ligand resulted from dmbg condensation with ammonia/hydrazine and formaldehyde) for applications in the treatment of infections produced by pathogenic microorganisms, including those complicated by biofilm development. [26] Based on these data, we report in this study the synthesis of a novel Cu(II) perchlorate complex with 1-(otolyl)biguanide and its complete characterization through single-crystal X-ray diffraction. The antimicrobial activity evaluation of the complex was evaluated against planktonic and adherent bacterial strains, and its biocompatibility was assessed against the L929 fibroblasts.…”

“…[ 25 ] Recent studies indicated that the biguanide incorporation into a macrocycle ligand generated promising complexes [CuL] (H 2 L: ligand resulted from dmbg condensation with ammonia/hydrazine and formaldehyde) for applications in the treatment of infections produced by pathogenic microorganisms, including those complicated by biofilm development. [ 26 ]…”