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Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity

A series of six heteroleptic copper(II) complexes with 2′-hydroxy-4-(dimethylamino)chalcone (HL) with the composition [Cu(N-N)(L)]NO(3) (1–6), where N-N stands for dmbpy = 5,5′-dimethyl-2,2′-bipyridine (1), bphen = 4,7-diphenyl-1,10-phenanthroline (2), dbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine (3),...

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Autores principales: Trávníček, Zdeněk, Malina, Tomáš, Vančo, Ján, Šebela, Marek, Dvořák, Zdeněk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967299/
https://www.ncbi.nlm.nih.gov/pubmed/36839630
http://dx.doi.org/10.3390/pharmaceutics15020307
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author Trávníček, Zdeněk
Malina, Tomáš
Vančo, Ján
Šebela, Marek
Dvořák, Zdeněk
author_facet Trávníček, Zdeněk
Malina, Tomáš
Vančo, Ján
Šebela, Marek
Dvořák, Zdeněk
author_sort Trávníček, Zdeněk
collection PubMed
description A series of six heteroleptic copper(II) complexes with 2′-hydroxy-4-(dimethylamino)chalcone (HL) with the composition [Cu(N-N)(L)]NO(3) (1–6), where N-N stands for dmbpy = 5,5′-dimethyl-2,2′-bipyridine (1), bphen = 4,7-diphenyl-1,10-phenanthroline (2), dbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine (3), nphen = 5-nitro-1,10-phenanthroline (4), bpy = 2,2′-bipyridine, (5), and dpa = 2,2′-dipyridylamine (6), was prepared and thoroughly characterized. The in vitro cytotoxicity screening on eight human cancer cell lines identified complex 2, containing the bulkiest N-donor ligands (bphen) as highly cytotoxic against cancer cells, with IC(50) values ranking from 1.0 to 2.3 μM, with good selectivity and low toxicity against healthy human fetal lung fibroblasts MRC-5. The cell-based assays, involving the most effective complex 2 in A2780 cancer cells, revealed its strong pro-apoptotic effects based on the effective activation of caspases 3/7, ROS overproduction, and autophagy in the A2780 cells while not impeding the cell cycle and mitochondrial membrane functions. The cellular uptake studies in A2780 and 22Rv1 cells uncovered no intracellular transport of the cationic complex 2, supporting the hypothesis that the in vitro anticancer effects of complex 2 are based on the combined extrinsic activation of apoptosis and autophagy induction.
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spelling pubmed-99672992023-02-26 Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity Trávníček, Zdeněk Malina, Tomáš Vančo, Ján Šebela, Marek Dvořák, Zdeněk Pharmaceutics Article A series of six heteroleptic copper(II) complexes with 2′-hydroxy-4-(dimethylamino)chalcone (HL) with the composition [Cu(N-N)(L)]NO(3) (1–6), where N-N stands for dmbpy = 5,5′-dimethyl-2,2′-bipyridine (1), bphen = 4,7-diphenyl-1,10-phenanthroline (2), dbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine (3), nphen = 5-nitro-1,10-phenanthroline (4), bpy = 2,2′-bipyridine, (5), and dpa = 2,2′-dipyridylamine (6), was prepared and thoroughly characterized. The in vitro cytotoxicity screening on eight human cancer cell lines identified complex 2, containing the bulkiest N-donor ligands (bphen) as highly cytotoxic against cancer cells, with IC(50) values ranking from 1.0 to 2.3 μM, with good selectivity and low toxicity against healthy human fetal lung fibroblasts MRC-5. The cell-based assays, involving the most effective complex 2 in A2780 cancer cells, revealed its strong pro-apoptotic effects based on the effective activation of caspases 3/7, ROS overproduction, and autophagy in the A2780 cells while not impeding the cell cycle and mitochondrial membrane functions. The cellular uptake studies in A2780 and 22Rv1 cells uncovered no intracellular transport of the cationic complex 2, supporting the hypothesis that the in vitro anticancer effects of complex 2 are based on the combined extrinsic activation of apoptosis and autophagy induction. MDPI 2023-01-17 /pmc/articles/PMC9967299/ /pubmed/36839630 http://dx.doi.org/10.3390/pharmaceutics15020307 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Trávníček, Zdeněk
Malina, Tomáš
Vančo, Ján
Šebela, Marek
Dvořák, Zdeněk
Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity
title Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity
title_full Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity
title_fullStr Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity
title_full_unstemmed Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity
title_short Heteroleptic Copper(II) Complexes Containing 2′-Hydroxy-4-(Dimethylamino)Chalcone Show Strong Antiproliferative Activity
title_sort heteroleptic copper(ii) complexes containing 2′-hydroxy-4-(dimethylamino)chalcone show strong antiproliferative activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967299/
https://www.ncbi.nlm.nih.gov/pubmed/36839630
http://dx.doi.org/10.3390/pharmaceutics15020307
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