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