Synthesis, biological evaluation and model membrane studies on metal complexes containing aromatic N,O-chelate ligands

Abstract

Novel lanthanide (Ln) compounds [Ln(L) 2 ]Cl . xH 2 O (Ln ¼ La 3þ , Ce 3þ , Sm 3þ ) containing aromatic N,O-chelate ligands [HL1 ¼ 4-amino-2-(1H-benzimidazol-2-yl)phenol; HL2 ¼ 5-amino-2-(1H-benzimidazol-2-yl)phenol] have been synthesized and structurally characterized by elemental analysis, NMR and IR spectroscopy, molar conductance measurements, and mass spectrometry (MS). The spectroscopic data suggested that the benzimidazolyl-phenol ligands act as N,O-chelate ligands through the iminic nitrogen and phenolic oxygen atoms. Elemental analysis indicated that lanthanide compounds were formed in a 1:2 stoichiometry (metal:ligand). In vitro biological evaluation was carried out using these complexes, exhibiting moderate cytotoxicity against six different human tumor cell lines (U251, human glioblastoma; HCT-15, colorectal carcinoma; MCF-7, breast epithelial adenocarcinoma; PC-3, prostate cancer; K562, myelogenous leukemia; SKLU-1, lung carcinoma) and lower toxicity against a non-cancerous cell line (COS-7, primate kidney). In addition, the antibacterial activity of the compounds was assessed against two gram-positive strains (Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115) and two gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27583) using the microdilution method. The results obtained show that the metal complexes exhibit higher biological activity than the free ligands, confirming a synergistic effect. Further benzimidazolyl-phenol derivatives were explored for the detection of bacteria using fluorescence imaging studies. Interestingly, the fluorescent properties of these compounds make them potential candidates to monitor the morphology of bacteria at different compound concentrations. Hence, the interaction of the ligand and complexes with model membranes mimicking those of bacteria was studied by using differential scanning calorimetry (DSC) and molecular dynamics (MD), showing that both compounds decreased the enthalpy of transition in two model membranes as the concentration of the compounds increased. In addition, the main transition temperature was slightly reduced as a result of these interactions.

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes

“…When comparing the results of the L1 and L2 series, a greater inhibitory effect was observed for the Schiff bases prepared from 2,4-dihydroxybenzaldehyde, which indicates that having an -OH functional group at the para- position of the salicyldene ring is very relevant for the biological behavior of this compound. The outcome of the substitution in the aminophenyl ring was also observed when comparing the results of the L2 series with those of the L4 series, revealing increased inhibitory activity for the 1,3-position compared with the 1,4-position, similar to the effect observed for the position of the amino group in N,O-chelate ligands derived from benzimidazolyl-phenol [ 40 ].…”

“…Additionally, the molecular docking studies discussed below indicated that the ligands could interact with molecular targets through hydrophilic bonds and conventional hydrogen bonds, in addition to pi-alkyl interactions with the three aromatic rings, which may also be the mechanisms involved in the inhibition of human DNA topoisomerase I [ 41 ]. Another selective target might be phosphatidylserine (anionic phospholipid), which is found on the outer membrane of cancerous cells and may electrostatically attract the positively charged ligand when in keto-enolic equilibria [ 40 ], as occurs for salen-type Schiff bases.…”

“…In a previous study, we demonstrated that compounds derived from benzimidazoles have the ability to slightly fluidize membrane models [ 40 ]. The increased fluidity may be accompanied by an increase in permeability [ 50 ], which could be responsible for the antiproliferative effects exerted by these compounds.…”

Atomic Layer Modulation of Multicomponent Thin Films through Combination of Experimental and Theoretical Approaches

“…The distance between two nodes was set to d (nm), and the surface area was set to (50 d ) 2 (nm 2 ). The sizes of each ligand and the precursors were modeled using the MOLview tool, − assuming a spherical model. The Carish and TMA precursors dissociated into *2O–Ru–2­[C 7 H 11 O 2 ] and *2O–Al­(CH 3 ) after surface adsorption through the loss of 2 CO ligands and 2 CH 3 groups, respectively.…”

A Study of the Interaction of a New Benzimidazole Schiff Base with Synthetic and Simulated Membrane Models of Bacterial and Mammalian Membranes

“…Studies including compounds with the benzimidazole motif on their structures are interesting for the scientific community, not only because of their known antibacterial and cytotoxic properties [ 18 , 19 , 20 ], but because of the high conjugation that they exhibit when forming Schiff bases, improving their electronic characteristics and often conferring fluorescent properties that facilitate the monitoring of morphology in microorganisms subjected to these types of drugs [ 21 ].…”