Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity
Melanoma is a skin cancer characterized by rapid growth and spread for which current therapies produce both resistance and increased risk of infection. To develop new anti-melanoma biocompatible species, the series of complexes Cu(N-N)(bzac)(X)⋅nH<sub>2</sub>O (N-N: 1,10-phenanthroline/2...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/1999-4923/14/8/1692 |
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| author | Rodica Olar Catalin Maxim Mihaela Badea Mihaela Bacalum Mina Raileanu Speranta Avram Nataša Čelan Korošin Teodora Burlanescu Arpad Mihai Rostas |
| author_facet | Rodica Olar Catalin Maxim Mihaela Badea Mihaela Bacalum Mina Raileanu Speranta Avram Nataša Čelan Korošin Teodora Burlanescu Arpad Mihai Rostas |
| author_sort | Rodica Olar |
| collection | DOAJ |
| description | Melanoma is a skin cancer characterized by rapid growth and spread for which current therapies produce both resistance and increased risk of infection. To develop new anti-melanoma biocompatible species, the series of complexes Cu(N-N)(bzac)(X)⋅nH<sub>2</sub>O (N-N: 1,10-phenanthroline/2,2′-bipyridine, Hbzac: 1-phenyl-1,3-butanedione, X: NO<sub>3</sub>/ClO<sub>4</sub>, and <i>n</i> = 0, 1) was studied. Single-crystal X-ray diffraction revealed a mononuclear structure for all complexes. The ability of the complexes to scavenge or trap reactive oxygen species such as O<sub>2</sub>⋅<sup>−</sup> and HO⋅ was proved by EPR spectroscopy experiments. All complexes inhibited B16 murine melanoma cells in a dose-dependent and nanomolar range, but the complexes with 1,10-phenanthroline were more active. Moreover, comparative activity on B16 and healthy BJ cells revealed a therapeutic index of 1.27–2.24. Bioinformatic methods were used to calculate the drug-likeness, pharmacokinetic, pharmacogenomic, and pharmacodynamic profiles of the compounds. The results showed that all compounds exhibit drug-likeness features, as well as promising absorption, distribution, metabolism, and excretion (ADME) properties, and no toxicity. The pharmacodynamics results showed that the neutral species appear to be good candidates for antitumor molecular targets (Tyrosyl-DNA phosphodiesterase 1, DNA-(apurinic or apyrimidinic site) lyase or Kruppel-like factor 5). Furthermore, the pharmacogenomic results showed a good affinity of the copper(II) complexes for the human cytochrome. These results recommend complexes bearing 1,10-phenanthroline as good candidates for developing drugs to melanoma alternative treatment. |
| first_indexed | 2024-03-09T03:57:42Z |
| format | Article |
| id | doaj.art-9b2aa9af9706452fbac396c16e5de735 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T03:57:42Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9b2aa9af9706452fbac396c16e5de7352023-12-03T14:17:51ZengMDPI AGPharmaceutics1999-49232022-08-01148169210.3390/pharmaceutics14081692Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma ActivityRodica Olar0Catalin Maxim1Mihaela Badea2Mihaela Bacalum3Mina Raileanu4Speranta Avram5Nataša Čelan Korošin6Teodora Burlanescu7Arpad Mihai Rostas8Faculty of Chemistry, Department of Inorganic Chemistry, University of Bucharest, 90-92 Panduri Str., 050663 Bucharest, RomaniaFaculty of Chemistry, Department of Inorganic Chemistry, University of Bucharest, 90-92 Panduri Str., 050663 Bucharest, RomaniaFaculty of Chemistry, Department of Inorganic Chemistry, University of Bucharest, 90-92 Panduri Str., 050663 Bucharest, RomaniaHoria Hulubei National Institute for Physics and Nuclear Engineering, Department of Life and Environmental Physics, 30 Reactorului Str., 077125 Magurele-Ilfov, RomaniaHoria Hulubei National Institute for Physics and Nuclear Engineering, Department of Life and Environmental Physics, 30 Reactorului Str., 077125 Magurele-Ilfov, RomaniaFaculty of Biology, Department of Anatomy, Animal Physiology and Biophysics, University of Bucharest, 91-95, Splaiul Independenței, 050095 Bucharest, RomaniaFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, SloveniaLaboratory of Optical Processes in Nanostructure Materials, National Institute of Materials Physics, 405A Atomiștilor Str., 077125 Magurele-Ilfov, RomaniaLaboratory of Atomic Structures and Defects in Advanced Materials, LASDAM, National Institute of Materials Physics, 405A Atomiștilor Str., 077125 Magurele-Ilfov, RomaniaMelanoma is a skin cancer characterized by rapid growth and spread for which current therapies produce both resistance and increased risk of infection. To develop new anti-melanoma biocompatible species, the series of complexes Cu(N-N)(bzac)(X)⋅nH<sub>2</sub>O (N-N: 1,10-phenanthroline/2,2′-bipyridine, Hbzac: 1-phenyl-1,3-butanedione, X: NO<sub>3</sub>/ClO<sub>4</sub>, and <i>n</i> = 0, 1) was studied. Single-crystal X-ray diffraction revealed a mononuclear structure for all complexes. The ability of the complexes to scavenge or trap reactive oxygen species such as O<sub>2</sub>⋅<sup>−</sup> and HO⋅ was proved by EPR spectroscopy experiments. All complexes inhibited B16 murine melanoma cells in a dose-dependent and nanomolar range, but the complexes with 1,10-phenanthroline were more active. Moreover, comparative activity on B16 and healthy BJ cells revealed a therapeutic index of 1.27–2.24. Bioinformatic methods were used to calculate the drug-likeness, pharmacokinetic, pharmacogenomic, and pharmacodynamic profiles of the compounds. The results showed that all compounds exhibit drug-likeness features, as well as promising absorption, distribution, metabolism, and excretion (ADME) properties, and no toxicity. The pharmacodynamics results showed that the neutral species appear to be good candidates for antitumor molecular targets (Tyrosyl-DNA phosphodiesterase 1, DNA-(apurinic or apyrimidinic site) lyase or Kruppel-like factor 5). Furthermore, the pharmacogenomic results showed a good affinity of the copper(II) complexes for the human cytochrome. These results recommend complexes bearing 1,10-phenanthroline as good candidates for developing drugs to melanoma alternative treatment.https://www.mdpi.com/1999-4923/14/8/1692Cu(II) complexstructureROScytotoxicitymelanoma cellsbioinformatics |
| spellingShingle | Rodica Olar Catalin Maxim Mihaela Badea Mihaela Bacalum Mina Raileanu Speranta Avram Nataša Čelan Korošin Teodora Burlanescu Arpad Mihai Rostas Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity Pharmaceutics Cu(II) complex structure ROS cytotoxicity melanoma cells bioinformatics |
| title | Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity |
| title_full | Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity |
| title_fullStr | Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity |
| title_full_unstemmed | Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity |
| title_short | Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity |
| title_sort | antiproliferative copper ii complexes bearing mixed chelating ligands structural characterization ros scavenging in silico studies and anti melanoma activity |
| topic | Cu(II) complex structure ROS cytotoxicity melanoma cells bioinformatics |
| url | https://www.mdpi.com/1999-4923/14/8/1692 |
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