New ternary Fe(III)-8-hydroxyquinoline–reduced Schiff base complexes as selective anticancer drug candidates

Ferretti, Valeria Alejandra; Matos, Carla; Canelas, Catarina; Pessoa, João Costa; Tomaz, Ana Isabel; Starosta, Radosław; Correia, Isabel; León, Ignacio E.

doi:10.1016/j.jinorgbio.2022.111961

Cited by 9 publications

(4 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our ongoing search for new anticancer drugs, we have developed different derivatives of 8-hydroxyquinolines (8HQ) and complexed them to different metal ions to take advantage of the synergistic effect of combining a bioactive organic moiety and biologically significant metals, such as copper, zinc, vanadium, iron, nickel, and ruthenium. − Coordination compounds present several advantages when compared to organic molecules since they may influence the size, charge, lipophilicity, and interaction with biomolecules, showing different coordination numbers and geometries and may also present redox activity. Our strategy explored the increase in the coordination ability of 8HQ by introducing substituents in the ortho position to the quinoline N atom while also containing donor groups in suitable positions to participate in the chelation of the metal ion.…”

Section: Introductionmentioning

confidence: 99%

Cu(II) and Zn(II) Complexes of New 8-Hydroxyquinoline Schiff Bases: Investigating Their Structure, Solution Speciation, and Anticancer Potential

et al. 2023

Self Cite

View full text Add to dashboard Cite

We report the synthesis and characterization of three novel Schiff bases (L1−L3) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with amines containing morpholine or piperidine moieties. These were reacted with CuCl 2 and ZnCl 2 yielding six new coordination compounds, with the general formula ML 2 , where M = Cu(II) or Zn(II) and L = L1−L3, which were all characterized by analytical, spectroscopic (Fourier transform infrared (FTIR), UV−visible absorption, nuclear magnetic resonance (NMR), or electron paramagnetic resonance (EPR)), and mass spectrometric techniques, as well as by singlecrystal X-ray diffraction. In the solid state, two Cu(II) complexes, with L1 and L2, are obtained as dinuclear compounds, with relatively short Cu−Cu distances (3.146 and 3.171 Å for Cu 2 (L1) 4 and Cu 2 (L2) 4 , respectively). The free ligands show moderate lipophilicity, while their complexes are more lipophilic. The pK a values of L1−L3 and formation constants of the complex (for ML and ML 2 ) species were determined by spectrophotometric titrations, with the Cu(II) complexes showing higher stability than the Zn(II) complexes. EPR indicated the presence of several species in solution as pH varied and binding modes were proposed. The binding of the complexes to bovine serum albumin (BSA) was evaluated by fluorescence and circular dichroism (CD) spectroscopies. All complexes bind BSA, and as demonstrated by CD, the process takes several hours to reach equilibrium. The antiproliferative activity was evaluated in malignant melanoma cells (A375) and in noncancerous keratinocytes (HaCaT). All complexes display significant cytotoxicity (IC 50 < 10 μM) but modest selectivity. The complexes show higher activity than the free ligands, the Cu(II) complexes being more active than the Zn(II) complexes, and approximately twice more cytotoxic than cisplatin. A Guava ViaCount assay corroborated the antiproliferative activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Cu(II) and Zn(II) Complexes of New 8-Hydroxyquinoline Schiff Bases: Investigating Their Structure, Solution Speciation, and Anticancer Potential

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Quinoline and its derivatives have wide biological and pharmacological applications, including anticancer and antimicrobial activity [31][32][33][34][35][36][37][38][39][40]. Similar diverse activity has also been shown by transition and other metal complexes of quinoline and its derivatives, such as 8-hydroxyquinoline (Figure 1) [41][42][43][44][45][46][47][48][49][50]. In contrast, quinones with redox properties similar to Q1, but without a chelating center, have shown much less cytotoxic activity toward cancer cells [5].…”

Section: Introductionmentioning

confidence: 93%

Increased Free Radical Generation during the Interaction of a Quinone-Quinoline Chelator with Metal Ions and the Enhancing Effect of Light

et al. 2023

View full text Add to dashboard Cite

Schiff bases and similar molecules forming metal complexes may cause redox effects, which may also be influenced by light. Anthraquinones such as doxorubicin and idarubicin are widely used antitumor agents, which can generate reactive oxygen species (ROS), stimulated by both the presence of iron and copper ions and also by light. The generated ROS can cause DNA scission, cell membrane oxidation, and many other toxic effects. The redox activity of the quinone-quinoline chelator 2-phenyl-4-(butylamino)naphtho [2,3-h]quinoline-7,12-dione (Q1) was investigated in the presence of iron, copper, and zinc. The influence of light in these interactions was also examined. The chemically induced dynamic nuclear polarization (CIDNP), nuclear magnetic resonance (NMR), and electron paramagnetic resonance (EPR) methods were used to elucidate the molecular changes and ROS generation effects of the Q1 metal interactions. A model electron transfer reaction system between 1,4-dihydropyridine and Q1 was utilized to demonstrate that the chelate complexes of Q1 with both Fe(III) and Cu(II) ions were more redox active than Q1 itself. Similarly, CIDNP and NMR data showed that the concentration dependence of the free radicals yield is much higher in the presence of Fe(III) and Cu(II) ions, in comparison to Zn(II), and also that it increased in the presence of light. These findings underline the role of transition metal ions and Q1 in cyclic redox chain reactions and increase the prospect of the development of copper- and iron-based chelating agents, including Q1 and its derivatives, for anticancer therapy. Furthermore, these findings also signify the effect of light on enhancing ROS formation by Q1 and the prospect of utilizing such information for designing target specific anticancer drugs for photodynamic therapy.

show abstract

“…47 Validation of the docking method through re-docking of naproxen to 4OR0 BSA was shown in one of our previous papers. 48…”

Section: Dft Calculations and Molecular Dockingmentioning

confidence: 99%

Enhanced selectivity towards melanoma cells with zinc(ii)-Schiff bases containing imidazole derivatives

Côrte-Real,

Sergi,

Yildirim

et al. 2024

Dalton Trans.

Self Cite

View full text Add to dashboard Cite

show abstract

New ternary Fe(III)-8-hydroxyquinoline–reduced Schiff base complexes as selective anticancer drug candidates

Cited by 9 publications

References 73 publications

Cu(II) and Zn(II) Complexes of New 8-Hydroxyquinoline Schiff Bases: Investigating Their Structure, Solution Speciation, and Anticancer Potential

Cu(II) and Zn(II) Complexes of New 8-Hydroxyquinoline Schiff Bases: Investigating Their Structure, Solution Speciation, and Anticancer Potential

Increased Free Radical Generation during the Interaction of a Quinone-Quinoline Chelator with Metal Ions and the Enhancing Effect of Light

Enhanced selectivity towards melanoma cells with zinc(ii)-Schiff bases containing imidazole derivatives

Contact Info

Product

Resources

About