Three Pt-Pt Complexes with Donor-acceptor Feature: Anticancer Activity, DNA Binding Studies and Molecular Docking Simulation.
Antineoplastic Agents
/ chemistry
Binding Sites
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cells, Cultured
DNA, Neoplasm
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Jurkat Cells
MCF-7 Cells
Molecular Docking Simulation
Molecular Structure
Organoplatinum Compounds
/ chemistry
Structure-Activity Relationship
Binuclear platinum (II) complexes
apoptosis
electrophoresis
flow cytometry
molecular docking
spectroscopic study.
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
03
2019
revised:
09
05
2019
accepted:
13
05
2019
pubmed:
4
7
2019
medline:
12
8
2020
entrez:
4
7
2019
Statut:
ppublish
Résumé
Due to their unique properties and potential applications in variety of areas, recently, a special attention is given to the binuclear platinum (II) complexes. They reveal a highly tunable features upon the modification of their cyclometallating and bridging ligands. The aim of this study was to evaluate the anticancer activity and DNA binding affinity of three binuclear platinum (II) complexes, including ht-[(p-FC MTT assay was performed to study the cell viability of Jurkat and MCF-7 lines against synthesized complexes, followed by apoptosis detection experiments. Several spectroscopic methods with molecular docking simulation were also used to investigate the detail of interaction of these platinum complexes with DNA. Cell viability assay demonstrated a notable level of cytotoxicity for the synthetic platinum complexes. Further studies proved that a pathway of cell signaling initiating the apoptosis might be activated by these complexes, particularly in the case of complexes 1 and 2. The results of both UV-visible and CD measurements showed the significant ability of these complexes to interact with DNA. While fluorescence data revealed that these complexes cannot enter DNA structure by intercalation, molecular docking assessment proved their DNA groove binding ability. The remarkable apoptosis inducing activity of the binuclear platinum complexes 1 and 2 and their considerable interaction with DNA suggest them as the potential antitumor medicines.
Sections du résumé
BACKGROUND
Due to their unique properties and potential applications in variety of areas, recently, a special attention is given to the binuclear platinum (II) complexes. They reveal a highly tunable features upon the modification of their cyclometallating and bridging ligands.
OBJECTIVE
The aim of this study was to evaluate the anticancer activity and DNA binding affinity of three binuclear platinum (II) complexes, including ht-[(p-FC
METHODS
MTT assay was performed to study the cell viability of Jurkat and MCF-7 lines against synthesized complexes, followed by apoptosis detection experiments. Several spectroscopic methods with molecular docking simulation were also used to investigate the detail of interaction of these platinum complexes with DNA.
RESULTS
Cell viability assay demonstrated a notable level of cytotoxicity for the synthetic platinum complexes. Further studies proved that a pathway of cell signaling initiating the apoptosis might be activated by these complexes, particularly in the case of complexes 1 and 2. The results of both UV-visible and CD measurements showed the significant ability of these complexes to interact with DNA. While fluorescence data revealed that these complexes cannot enter DNA structure by intercalation, molecular docking assessment proved their DNA groove binding ability.
CONCLUSION
The remarkable apoptosis inducing activity of the binuclear platinum complexes 1 and 2 and their considerable interaction with DNA suggest them as the potential antitumor medicines.
Identifiants
pubmed: 31267879
pii: ACAMC-EPUB-99340
doi: 10.2174/1871520619666190702114211
doi:
Substances chimiques
Antineoplastic Agents
0
DNA, Neoplasm
0
Organoplatinum Compounds
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1762-1774Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.