期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 235, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2022.111932
关键词
Oxidovanadium(IV) complexes; 8-hydroxyquinoline derivatives; Schiff bases; Solution stability; Speciation; Anticancer
资金
- Fundacao para a Ciencia e Tecnologia (FCT) [UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020]
- Programa Operacional Regional de Lisboa
- FCT [SFRH/BD/135797/2018]
- Portuguese-Hungarian Scientific & Technological Cooperation [TET-PT-2018-00002, UNKP-21-3-SZTE-455]
- New National Excellence Program Ministry of Human Capacities
- `Lendulet' Programme (ELKH) [LP2019-6/2019]
- COST Action [CA18202]
- NECTAR-Network for Equilibria and Chemical Thermodynamics Advanced Research
- Koc University School of Medicine (KUSOM)
- Presidency of Turkey, Presidency of Strategy and Budget
- Fondazione di Sardegna [FdSGarribba2017]
- Regione Autonoma della Sardegna [RASSR79857]
- MICINN' Juan de la Cierva program [FJC2019-039135-I]
- Fundacao para a Ciencia e a Tecnologia, MCTES (FCT/MCTES) [UIDB/50006/2020, UIDP/50006/2020]
- [PTDC/QUI-QIN/0586/2020]
- Fundação para a Ciência e a Tecnologia [PTDC/QUI-QIN/0586/2020, UIDP/50006/2020, SFRH/BD/135797/2018] Funding Source: FCT
We reported the synthesis and characterization of a family of benzohydrazones and their oxidovanadium(IV) complexes. The complexes showed high antiproliferative activity in cancer cells, possibly through oxidative stress-induced DNA damage and apoptosis.
We report the synthesis and characterization of a family of benzohydrazones (L-n, n = 1-6) derived from 2-car-baldehyde-8-hydroxyquinoline and benzylhydrazides containing different substituents in the para position. Their oxidovanadium(IV) complexes were prepared and compounds with 1:1 and 1:2 metal-to-ligand stoichiometry were obtained. All compounds were characterized by elemental analyses and mass spectrometry as well as FTIR, UV-visible absorption, NMR (ligand precursors) and EPR (complexes) spectroscopies, and by DFT computational methods. Proton dissociation constants, lipophilicity and solubility in aqueous media were determined for all ligand precursors. Complex formation with V(IV)O was evaluated by spectrophotometry for L-4 (Me-substituted) and L-6 (OH-substituted) and formation constants for mono [VO(HL)](+), [VO(L)] and bis [VO(HL)(2)], [VO(HL) (L)], [VO(L)(2)](2- )complexes were determined. EPR spectroscopy indicates the formation of [VO(HL)](+) and [VO (HL)(2)], with this latter being the major species at the physiological pH. Noteworthy, the EPR data suggest a different behaviour for L-4 and L-6, which confirm the results obtained in the solid state. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. All complexes show much higher activity on A-375 (IC50 < 6.3 mu M) than in A-549 cells (IC50 > 20 mu M). Complex 3 (F-substituted) shows the lowest IC50 on both cell lines and lower than cisplatin (in A-375). Studies identified this compound as the one showing the highest increase in Annexin-V staining, caspase activity and induction of double stranded breaks, corroborating the cytotoxicity results. The mechanism of action of the complexes involves reactive oxygen species (ROS) induced DNA damage, and cell death by apoptosis.
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