New AlIIIZnII and AlIIICuII dinuclear complexes: Phosphatase-like activity and cytotoxicity

J Inorg Biochem. 2021 Jun:219:111392. doi: 10.1016/j.jinorgbio.2021.111392. Epub 2021 Mar 13.

Abstract

Herein, we report the synthesis and characterization of the first two AlIII(μ-OH)MII (M = Zn (1) and Cu (2)) complexes with the unsymmetrical ligand H2L{2-[[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl]-6-bis(pyridylmethyl)aminomethyl}-4-methylphenol. The complexes were characterized through elemental analysis, X-ray crystallography, IR spectroscopy, mass spectrometry and potentiometric titration. In addition, complex 2 was characterized by electronic spectroscopy. Kinetics studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate by 1 and 2 show Michaelis-Menten behavior, with 1 being slightly more active (8.31%) than 2 (at pH 7.0). The antimicrobial effect of the compounds was studied using four bacterial strains (Staphylococcus aureus, Pseudomonas aeuruginosa, Shigella sonnei and Shigella dysenteriae) and for both complexes the inhibition of bacterial growth was superior to that caused by sulfapyridine, but inferior to that of tetracycline. The dark cytotoxicity and photocytotoxicity (under UV-A light) of the complexes in a chronic myelogenous leukemia cell line were investigated. Complexes 1 and 2 exhibited significant cytotoxic activity against K562 cells, which undergoes a 2-fold increase on applying 5 min of irradiation with UV-A light. Complex 2 was more effective and a good correlation between cytotoxicity and intracellular concentration was observed, the intracellular copper concentration required to inhibit 50% of cell growth being 3.5 × 10-15 mol cell-1.

Keywords: Aluminum complexes; Cytotoxicity activity in cancer cells; Phosphatase-like activity.

MeSH terms

  • Aluminum / chemistry
  • Aluminum / pharmacology*
  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Bacteria / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Copper / chemistry
  • Copper / pharmacology*
  • Crystallography, X-Ray / methods
  • Humans
  • Hydrolysis
  • K562 Cells
  • Kinetics
  • Ligands
  • Mass Spectrometry / methods
  • Phosphoric Monoester Hydrolases / metabolism*
  • Zinc / chemistry
  • Zinc / pharmacology*

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Ligands
  • Copper
  • Aluminum
  • Phosphoric Monoester Hydrolases
  • Zinc