In vitro and in vivo anticancer activity of tridentate thiosemicarbazone copper complexes: Unravelling an unexplored pharmacological target.
Animals
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Mice
Mice, Inbred C57BL
Models, Molecular
Molecular Structure
Neoplasms, Experimental
/ drug therapy
Organometallic Compounds
/ chemical synthesis
Structure-Activity Relationship
Thiosemicarbazones
/ chemical synthesis
Tumor Cells, Cultured
Anticancer compounds
Copper complexes
Nanomolar activity
Protein disulfide isomerase inhibitors
Thiosemicarbazones
X-ray structure
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 May 2020
15 May 2020
Historique:
received:
18
12
2019
revised:
16
03
2020
accepted:
20
03
2020
pubmed:
6
4
2020
medline:
1
12
2020
entrez:
6
4
2020
Statut:
ppublish
Résumé
Certain metal complexes can have a great antitumor activity, as the use of cisplatin in therapy has been demonstrating for the past fifty years. Copper complexes, in particular, have attracted much attention as an example of anticancer compounds based on an endogenous metal. In this paper we present the synthesis and the activity of a series of copper(II) complexes with variously substituted salicylaldehyde thiosemicarbazone ligands. The in vitro activity of both ligands and copper complexes was assessed on a panel of cell lines (HCT-15, LoVo and LoVo oxaliplatin resistant colon carcinoma, A375 melanoma, BxPC3 and PSN1 pancreatic adenocarcinoma, BCPAP thyroid carcinoma, 2008 ovarian carcinoma, HEK293 non-transformed embryonic kidney), highlighting remarkable activity of the metal complexes, in some cases in the low nanomolar range. The copper(II) complexes were also screened, with good results, against 3D spheroids of colon (HCT-15) and pancreatic (PSN1) cancer cells. Detailed investigations on the mechanism of action of the copper(II) complexes are also reported: they are able to potently inhibit Protein Disulfide Isomerase, a copper-binding protein, that is recently emerging as a new therapeutic target for cancer treatment. Good preliminary results obtained in C57BL mice indicate that this series of metal-based compounds could be a very promising weapon in the fight against cancer.
Identifiants
pubmed: 32248006
pii: S0223-5234(20)30233-6
doi: 10.1016/j.ejmech.2020.112266
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Organometallic Compounds
0
Thiosemicarbazones
0
copper-thiosemicarbazone complex
127913-88-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112266Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no competing financial interest.