Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole
Nádia Ribeiro,
Pedro F. Farinha,
Jacinta O. Pinho,
Hugo Luiz,
János P. Mészáros,
Adelino M. Galvão,
João Costa Pessoa,
Éva A. Enyedy,
Catarina Pinto Reis,
Isabel Correia,
Maria Manuela Gaspar
Affiliations
Nádia Ribeiro
Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
Pedro F. Farinha
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
Jacinta O. Pinho
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
Hugo Luiz
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
János P. Mészáros
MTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
Adelino M. Galvão
Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
João Costa Pessoa
Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
Éva A. Enyedy
MTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary
Catarina Pinto Reis
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
Isabel Correia
Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
Maria Manuela Gaspar
Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
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 (H2L) 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)2Cl(H2O)]. 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 IC50 < 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.
