Cu(ii) and V(iv)O complexes with tri- or tetradentate ligands based on (2-hydroxybenzyl)-l-alanines reveal promising anticancer therapeutic potential.
Dalton Trans
; 50(1): 157-169, 2021 Jan 07.
Article
em En
| MEDLINE
| ID: mdl-33290472
ABSTRACT
Four new ligand precursors (H2L1-H2L4), derived from the Mannich condensation of two amino acids (l-Val and l-Phe) and two 3,5-disubstituted phenols (t-Bu or Me), and the corresponding oxidovanadium(iv) (1-4) and copper(ii) (6-7) complexes are synthesized. Two other related compounds (H2L5 and H2L6), containing an additional 2-methyl-pyridine arm, and the corresponding VIVO (5) and CuII (8-9) complexes were also obtained. All metal complexes are monomeric in the solid state, having a solvent molecule or a chloride ion in the coordination sphere. The in vitro cytotoxic activity of all compounds is evaluated against cancer cells from different origins. The IC50 values at 72 h are in the range of 6-15 µM for HeLa cells, 4-17 µM for A-549 cells and >25 µM for MDA-MB-231 cells, except for [VIVOL1(CH3OH)] (1) and [CuL6(H2O)] (9). With the exception of H2L6, overall, the metal complexes are more cytotoxic than the corresponding ligand precursors. Globally, the cellular viability data show that (i) the l-Phe derived compounds are more cytotoxic than the corresponding l-Val complexes; (ii) the presence of the bulkier t-Bu groups increases the cytotoxicity; (iii) the presence of a 2-methyl-pyridine arm increases considerably the cytotoxicity; and (iv) the CuII-complexes are more cytotoxic than the VIVO-compounds. Complexes [VIVOL3(CH3OH)] (3), [CuL3(H2O)] (7) and [CuL5(H2O)] (8) were further evaluated and their mechanism of action was determined to be apoptosis, evidenced by AnnexinV staining and the increase in caspase 3/7 activity. Compounds 3, 7 and 8 also exhibit DNA cleavage activity, involving the formation of reactive oxygen species and were able to induce genomic damage in cells as determined by COMET assay.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
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Fenilalanina
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Valina
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Vanadatos
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Cobre
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Complexos de Coordenação
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article