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

Alberto Aragón-Muriel; Yamil Liscano-Martínez; Ernesto Rufino-Felipe; David Morales-Morales; Jose Oñate-Garzón; Dorian Polo-Cerón

doi:10.1016/j.heliyon.2020.e04126

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

Heliyon. 2020 Jun 7;6(6):e04126. doi: 10.1016/j.heliyon.2020.e04126. eCollection 2020 Jun.

Authors

Alberto Aragón-Muriel¹, Yamil Liscano-Martínez², Ernesto Rufino-Felipe³, David Morales-Morales³, Jose Oñate-Garzón⁴, Dorian Polo-Cerón¹

Affiliations

¹ Laboratorio de Investigación en Catálisis y Procesos (LICAP), Facultad de Ciencias Naturales y Exactas, Departamento de Química, Universidad del Valle, Cali 760001, Colombia.
² Grupo de Genética, Regeneración y Cáncer, Facultad de Ciencias Naturales y Exactas, Instituto de Biología, Universidad de Antioquia, Medellín 050010, Colombia.
³ Instituto de Química, Universidad Nacional Autónoma de México, Cd. Universitaria, Circuito Exterior, Coyoacán, México DF 04510, Mexico.
⁴ Grupo de Investigación en Química y Biotecnología (QUIBIO), Facultad de Ciencias Básicas, Universidad Santiago de Cali, Cali 760031, Colombia.

Abstract

Novel lanthanide (Ln) compounds [Ln(L)₂]Cl^.xH₂O (Ln = La³⁺, Ce³⁺, Sm³⁺) containing aromatic N,O-chelate ligands [HL1 = 4-amino-2-(1H-benzimidazol-2-yl)phenol; HL2 = 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.

Keywords: Antibacterial activity; Benzimidazole; Cancer; Cytotoxicity; Fluorescence; Inorganic chemistry; Lanthanide complexes; Model membranes; Molecular dynamics.