Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole.
Nádia RibeiroPedro F FarinhaJacinta Oliveira PinhoHugo LuizJános P MészárosAdelino M GalvãoJoão Costa PessoaÉva A EnyedyCatarina Pinto ReisIsabel CorreiaMaria Manuela GasparPublished in: Pharmaceutics (2022)
Designing new metallodrugs for anticancer therapy is a driving force in the scientific community. Aiming to contribute to this field, we hereby report the development of a Schiff base (H 2 L) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with 2-hydrazinobenzothiazole and its complexation with transition metal ions. All compounds were characterised by analytical and spectroscopic techniques, which disclosed their structure: [Cu(HL)Cl], [Cu(HL) 2 ], [Ni(HL)(acetate)], [Ni(HL) 2 ], [Ru(HL)Cl(DMSO)], [VO(HL) 2 ] and [Fe(HL) 2 Cl(H 2 O)]. Different binding modes were proposed, showing the ligand's coordination versatility. The ligand proton dissociation constants were determined, and the tested compounds showed high lipophilicity and light sensitivity. The stability of all complexes in aqueous media and their ability to bind to albumin were screened. Based on an antiproliferative in vitro screening, [Ni(HL)(acetate)] and [Ru(HL)Cl(DMSO)] were selected for further studies aiming to investigate their mechanisms of action and therapeutic potential towards colon cancer. The complexes displayed IC 50 < 21 μM towards murine (CT-26) and human (HCT-116) colon cancer cell lines. Importantly, both complexes exhibited superior antiproliferative properties compared to the clinically approved 5-fluorouracil. [Ni(HL)(acetate)] induced cell cycle arrest in S phase in CT-26 cells. For [Ru(HL)Cl(DMSO)] this effect was observed in both colon cancer cell lines. Additionally, both compounds significantly inhibited cell migration particularly in the human colon cancer cell line, HCT-116. Overall, the therapeutic potential of both metal complexes was demonstrated.
Keyphrases
- cell cycle arrest
- transition metal
- endothelial cells
- cell death
- cell migration
- healthcare
- metal organic framework
- pi k akt
- mental health
- magnetic resonance imaging
- magnetic resonance
- transcription factor
- oxidative stress
- induced pluripotent stem cells
- cell proliferation
- binding protein
- dna binding
- electron transfer
- dual energy