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

被引:1
|
作者
Mojaddami, Ayyub [1 ,2 ]
Abedanzadeh, Sedigheh [3 ]
Bagherzadeh, Mehrafarin [2 ]
Foroutan, Gisou [2 ]
Khodayar, Mohammad Javad [1 ]
Panahimehr, Mohammad [4 ]
Fereidoonnezhad, Masood [1 ,2 ]
机构
[1] Ahvaz Jundishapur Univ Med Sci, Med Basic Sci Res Inst, Toxicol Res Ctr, Ahvaz, Iran
[2] Ahvaz Jundishapur Univ Med Sci, Fac Pharm, Dept Med Chem, Ahvaz, Iran
[3] Kharazmi Univ, Fac Chem, Tehran 1571914911, Iran
[4] Ayatollah Boroujerdi Univ, Fac Basic Sci, Dept Chem, Boroujerd, Iran
关键词
platinum(II) complexes; 2-(diphenylphosphino)pyridine ligand; molecular docking; DNA interaction; apoptosis; ROS; BIOLOGICAL EVALUATION; STRUCTURAL-CHARACTERIZATION; CANCER-THERAPY; DERIVATIVES; REACTIVITY; CISPLATIN; DESIGN;
D O I
10.1002/cbdv.202201177
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Platinum-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 & mu;M, respectively, which were significantly better than that observed for cisplatin (19.02, and 8.64 & mu;M). 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.
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页数:9
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