title: Synthesis, Biological Evaluation, and Molecular Docking Studies on the DNA Binding Interactions of Platinum(II) Rollover Complexes Containing Phosphorus Donor Ligands.
abstract: Cyclometalated rollover complexes of the type [PtMe(κ2N,C-bipyO-H)(L)] [bipyO-H=cyclometalated 2,2'-bipyridine N-oxide; L=tricyclohexylphosphine (PCy3, 2 a), 2-(diphenylphosphino)pyridine (PPh2py, 2 b), P(OPh)3(2 c)] were synthesized by treating [PtMe(κ2N,C-bipyO-H)(SMe2)] (1) with various monodentate phosphine and phosphite ligands. These complexes were characterized by NMR spectroscopy, and the structure of 2 a was confirmed by single-crystal X-ray diffraction. Complex 1 was treated with bis(diphenylphosphino)methane (dppm) at a 1:1 ratio to give the corresponding [PtMe(κ2N,C-bipyO-H)(κ1P-dppm)] (3 b) complex, in which the dppm ligand acts as a monodentate pendant ligand. The biological activities of these complexes were evaluated against a panel of four standard cancer cell lines: lung carcinoma (A549), ovarian carcinoma (OV-90 and SKOV3), and breast carcinoma (MCF-7). Complexes 2 c and especially 3 b indicated effective potent cytotoxic activity regarding the cell lines. Electrophoresis mobility shift assays and molecular-modeling investigations were performed to determine the specific binding mode and the binding orientation of these alkylating agents to DNA. Detection of cellular reactive oxygen species was also determined.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.|Cancer, Environmental and Petroleum Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Masood
authors.initials: M
authors.lastname: Fereidoonnezhad
authors.affiliation: Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Yousef Sobouti Blvd., Zanjan, 45137-6731, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Niazi
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Shahmohammadi Beni
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Faghih
authors.affiliation: Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Faghih
authors.affiliation: Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Yousef Sobouti Blvd., Zanjan, 45137-6731, Iran.
authors.forename: Hamid R
authors.identifier: 0000-0002-2579-2185
authors.initials: HR
authors.lastname: Shahsavari
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000072283:A549 Cells; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010984:Platinum / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D056831:Coordination Complexes; D017382:Reactive Oxygen Species; D010984:Platinum; D015082:2,2'-Dipyridyl; D004247:DNA
keywords: DNA; P ligands; biological activity; molecular docking; platinum