Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole
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<sub>2</sub>L) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with 2-hydrazinobenz...
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/12/2583 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nádia Ribeiro |
| collection | DOAJ |
| description | 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<sub>2</sub>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)<sub>2</sub>], [Ni(HL)(acetate)], [Ni(HL)<sub>2</sub>], [Ru(HL)Cl(DMSO)], [VO(HL)<sub>2</sub>] and [Fe(HL)<sub>2</sub>Cl(H<sub>2</sub>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<sub>50</sub> < 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. |
| first_indexed | 2024-03-09T15:58:55Z |
| format | Article |
| id | doaj.art-f9f1ad84488c47f4a07178de2132bd10 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T15:58:55Z |
| publishDate | 2022-11-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-f9f1ad84488c47f4a07178de2132bd102023-11-24T17:18:28ZengMDPI AGPharmaceutics1999-49232022-11-011412258310.3390/pharmaceutics14122583Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and BenzothiazoleNádia Ribeiro0Pedro F. Farinha1Jacinta O. Pinho2Hugo Luiz3János P. Mészáros4Adelino M. Galvão5João Costa Pessoa6Éva A. Enyedy7Catarina Pinto Reis8Isabel Correia9Maria Manuela Gaspar10Centro 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, PortugalResearch Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, PortugalResearch Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, PortugalResearch Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, PortugalMTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, HungaryCentro 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, PortugalCentro 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, PortugalMTA-SZTE Lendület Functional Metal Complexes Research Group, Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, HungaryResearch Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, PortugalCentro 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, PortugalResearch Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, PortugalDesigning 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<sub>2</sub>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)<sub>2</sub>], [Ni(HL)(acetate)], [Ni(HL)<sub>2</sub>], [Ru(HL)Cl(DMSO)], [VO(HL)<sub>2</sub>] and [Fe(HL)<sub>2</sub>Cl(H<sub>2</sub>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<sub>50</sub> < 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.https://www.mdpi.com/1999-4923/14/12/2583metal complexeshydrazoneproton dissociation constantsalbumin bindingcolorectal cancerin vitro studies |
| spellingShingle | 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 Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole Pharmaceutics metal complexes hydrazone proton dissociation constants albumin binding colorectal cancer in vitro studies |
| title | Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole |
| title_full | Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole |
| title_fullStr | Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole |
| title_full_unstemmed | Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole |
| title_short | Metal Coordination and Biological Screening of a Schiff Base Derived from 8-Hydroxyquinoline and Benzothiazole |
| title_sort | metal coordination and biological screening of a schiff base derived from 8 hydroxyquinoline and benzothiazole |
| topic | metal complexes hydrazone proton dissociation constants albumin binding colorectal cancer in vitro studies |
| url | https://www.mdpi.com/1999-4923/14/12/2583 |
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