ROS‐Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2‐(Diphenylphosphino)pyridine Ligands

Author:

Mojaddami Ayyub12,Abedanzadeh Sedigheh3,Bagherzadeh Mehrafarin2,Foroutan Gisou2,Khodayar Mohammad Javad1,Panahimehr Mohammad4,Fereidoonnezhad Masood12ORCID

Affiliation:

1. Toxicology Research Center Medical Basic Sciences Research Institute Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran

2. Department of Medicinal Chemistry Faculty of Pharmacy Ahvaz Jundishapur University of Medical Sciences Ahvaz Iran

3. Faculty of Chemistry Kharazmi University Tehran 15719-14911 Iran

4. Department of Chemistry Faculty of Basic Science Ayatollah Boroujerdi University Boroujerd Iran

Abstract

AbstractPlatinum‐based drugs have been widely used in cancer treatment. However, their severe side effects have limited their use. So, researchers have been striving to find compounds with fewer side effects and greater efficacy, to overcome these drawbacks. Here, the cytotoxicity of platinum(II) complexes containing 2‐(diphenylphosphino)pyridine ligands have been studied on human lung (A549), ovarian (SKOV3), breast (MCF‐7) cancer, and normal breast (MCF‐10A) cell lines. The most potent compound exhibits a marked cell growth‐inhibitory effect against ovarian and lung cancer cells with IC50 values of 9.41 and 5.58 μM, respectively, which were significantly better than that observed for cisplatin (19.02, and 8.64 μM). Additionally, all complexes achieved significantly lower cytotoxicity towards MCF‐10A. To investigate the interaction of complexes with DNA, an electrophoresis mobility shift assay was conducted, which indicated that complexes bind to DNA and affect its electrophoretic mobility. An analysis of apoptosis in A549 cells supported the conclusion that they inhibits cell proliferation via induction of apoptosis in a concentration‐dependent manner. Molecular docking was also used to investigate the interactions of compounds with different DNA structures. These compounds have the ability to be a suitable pharmaceutical compound with further investigations in the field of cancer research.

Funder

Ahvaz Jundishapur University of Medical Sciences

Publisher

Wiley

Subject

Molecular Biology,Molecular Medicine,General Chemistry,Biochemistry,General Medicine,Bioengineering

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