DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes

DNA has become the target of metal complexes in cancer drug discovery. Due to the side effects of widely known cisplatin and its derivative compounds, alternative metal-based drug discovery studies are still ongoing. In this study, the DNA-binding ability of Pd(II) and Pt(II) complexes of four phosp...

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Main Authors: Burcu Saygıdeğer Demir, Simay İnce, Mustafa Kemal Yilmaz, Aycan Sezan, Ezgi Derinöz, Tugba Taskin-Tok, Yasemin Saygideger
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/11/2409
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author Burcu Saygıdeğer Demir
Simay İnce
Mustafa Kemal Yilmaz
Aycan Sezan
Ezgi Derinöz
Tugba Taskin-Tok
Yasemin Saygideger
author_facet Burcu Saygıdeğer Demir
Simay İnce
Mustafa Kemal Yilmaz
Aycan Sezan
Ezgi Derinöz
Tugba Taskin-Tok
Yasemin Saygideger
author_sort Burcu Saygıdeğer Demir
collection DOAJ
description DNA has become the target of metal complexes in cancer drug discovery. Due to the side effects of widely known cisplatin and its derivative compounds, alternative metal-based drug discovery studies are still ongoing. In this study, the DNA-binding ability of Pd(II) and Pt(II) complexes of four phosphorus Schiff base ligands and four hydrazonoic-phosphines are investigated by using in silico analyses. Phosphorus Schiff base-Pd(II) complexes encoded as <b>B1</b> and <b>B2</b> with the best DNA-binding potential are synthesized and characterized. The DNA-binding potentials of these two new Pd(II) complexes are also investigated experimentally, and their antitumor properties are demonstrated in vitro in A549, MCF7, HuH7, and HCT116 cancer cells. The mechanisms of these metal complexes that kill the cells mentioned above in different activities are elucidated by flow cytometry apoptosis analysis and colony formation analysis The in silico binding energies of these two new palladium complexes ΔG (<b>B1</b>): −4.51 and ΔG (<b>B2</b>): −6.04 kcal/mol, and their experimental DNA-binding constants were found as Kb (<b>B1</b>): 4.24 × 10<sup>5</sup>, Kb (<b>B2</b>): 4.98 × 10<sup>5</sup>). The new complexes, which show different antitumor effects in different cells, are the least effective in HuH7 liver cells, while they showed the best antitumor properties in HCT116 colon cancer cells.
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spelling doaj.art-c07aaff794e34509ad22ea2de7a9e2c82023-11-24T06:21:48ZengMDPI AGPharmaceutics1999-49232022-11-011411240910.3390/pharmaceutics14112409DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal ComplexesBurcu Saygıdeğer Demir0Simay İnce1Mustafa Kemal Yilmaz2Aycan Sezan3Ezgi Derinöz4Tugba Taskin-Tok5Yasemin Saygideger6Department of Biotechnology, Institute of Natural and Applied Sciences, Çukurova University, Adana 01330, TurkeyDepartment of Nanotechnology and Advanced Materials, Institute of Science and Technology, Mersin University, Mersin 33343, TurkeyDepartment of Nanotechnology and Advanced Materials, Institute of Science and Technology, Mersin University, Mersin 33343, TurkeyDepartment of Biotechnology, Institute of Natural and Applied Sciences, Çukurova University, Adana 01330, TurkeyDepartment of Biotechnology, Institute of Natural and Applied Sciences, Çukurova University, Adana 01330, TurkeyDepartment of Chemistry, Faculty of Arts and Science, Gaziantep University, Gaziantep 27410, TurkeyDepartment of Biotechnology, Institute of Natural and Applied Sciences, Çukurova University, Adana 01330, TurkeyDNA has become the target of metal complexes in cancer drug discovery. Due to the side effects of widely known cisplatin and its derivative compounds, alternative metal-based drug discovery studies are still ongoing. In this study, the DNA-binding ability of Pd(II) and Pt(II) complexes of four phosphorus Schiff base ligands and four hydrazonoic-phosphines are investigated by using in silico analyses. Phosphorus Schiff base-Pd(II) complexes encoded as <b>B1</b> and <b>B2</b> with the best DNA-binding potential are synthesized and characterized. The DNA-binding potentials of these two new Pd(II) complexes are also investigated experimentally, and their antitumor properties are demonstrated in vitro in A549, MCF7, HuH7, and HCT116 cancer cells. The mechanisms of these metal complexes that kill the cells mentioned above in different activities are elucidated by flow cytometry apoptosis analysis and colony formation analysis The in silico binding energies of these two new palladium complexes ΔG (<b>B1</b>): −4.51 and ΔG (<b>B2</b>): −6.04 kcal/mol, and their experimental DNA-binding constants were found as Kb (<b>B1</b>): 4.24 × 10<sup>5</sup>, Kb (<b>B2</b>): 4.98 × 10<sup>5</sup>). The new complexes, which show different antitumor effects in different cells, are the least effective in HuH7 liver cells, while they showed the best antitumor properties in HCT116 colon cancer cells.https://www.mdpi.com/1999-4923/14/11/2409molecular dockingphosphorus Schiff basemetal complexescancer cellsantitumorDNA binding
spellingShingle Burcu Saygıdeğer Demir
Simay İnce
Mustafa Kemal Yilmaz
Aycan Sezan
Ezgi Derinöz
Tugba Taskin-Tok
Yasemin Saygideger
DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
Pharmaceutics
molecular docking
phosphorus Schiff base
metal complexes
cancer cells
antitumor
DNA binding
title DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
title_full DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
title_fullStr DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
title_full_unstemmed DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
title_short DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes
title_sort dna binding and anticancer properties of new pd ii phosphorus schiff base metal complexes
topic molecular docking
phosphorus Schiff base
metal complexes
cancer cells
antitumor
DNA binding
url https://www.mdpi.com/1999-4923/14/11/2409
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