Dual anticancer and antibacterial activities of bismuth compounds based on asymmetric [NN'O] ligands

Abstract

Two new bismuth(III) complexes, [BiL1Cl2] (1) and [BiL2Cl2] (2), in which L1 is (2-hydroxy-4-6-di-tert-butylbenzyl-2-pyridylmethyl)amine and L2 is 2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol, were synthesized and characterized by elemental and conductivity analyses, atomic absorption spectrometry, infrared and 1H NMR spectroscopies. The molecular structure of 1 reveals that the NN'O ligand forms a 1:1 complex with bismuth through coordination via the nitrogen of the aliphatic amine, the nitrogen of the pyridine ring and the oxygen of the phenolate. The coordination sphere is completed with two chloride anions in a distorted square pyramidal geometry. Bismuth exhibits the same coordination mode in compound 2. The cytotoxic activity of 1 and 2 was investigated in a chronic myelogenous leukemia cell line. The complexes are approximately three times more potent than the corresponding free ligands, with the IC50 values 0.30 and 0.38 μM for complex 1 and 2, respectively. To address the cellular mechanisms underlying cell demise, apoptosis was quantified by flow cytometry analysis. From 0.1 μM, both complexes induce apoptosis and there is a remarkable concentration-dependent increase in the population of cells in apoptosis. The complexes were also evaluated against Gram-positive and Gram-negative bacteria. Both inhibited the bacterial growth in a concentration-dependent way, with remarkable activity in some of the tested strains, for example, complex 2 was more active than its free ligand against all bacterial strains and approximately fourteen times more potent against S. dysenteriae and S. typhimurium.