Anticancer activity assessment of two novel binuclear platinum (II) complexes.
In the current study, two binuclear Pt (II) complexes, containing cis, cis-[Me2Pt (μ-NN) (μ-dppm) PtMe2] (1), and cis,cis-[Me2Pt(μ-NN)(μ dppm) Pt((CH2)4)] (2) in which NN=phthalazine and dppm=bis (diphenylphosphino) methane were evaluated for their anticancer activities and DNA/purine nucleotide binding properties. These Pt (II) complexes, with the non-classical structures, demonstrated a significant anticancer activity against Jurkat and MCF-7 cancer cell lines. The results of ethidium bromide/acridine orange staining and Caspase-III activity suggest that these complexes were capable to stimulate an apoptotic mechanism of cell death in the cancer cells. Using different biophysical techniques and docking simulation analysis, we indicated that these complexes were also capable to interact efficiently with DNA via a non-intercalative mechanism. According to our results, substitution of cyclopentane (in complex 2) with two methyl groups (in complex 1) results in significant improvement of the complex ability to interact with DNA and subsequently to induce the anticancer activity. Overall, these binuclear Pt (II) complexes are promising group of the non-classical potential anticancer agents which can be considered as molecular templates in designing of highly efficient platinum anticancer drugs.
Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran; Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
Mohammad Bagher
MB
Shahsavani
Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
Shamseddin
S
Ahmadi
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
Marzieh Dadkhah
MD
Aseman
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
S Masoud
SM
Nabavizadeh
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
Mehdi
M
Rashidi
Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
Zahra
Z
Asadi
Institute for Cancer Research (ICR), School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Nasrollah
N
Erfani
Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
Atiyeh
A
Ghasemi
Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
Ali Akbar
AA
Saboury
Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Ali
A
Niazi
Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
Aminollah
A
Bahaoddini
Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran. Electronic address: ryousefi@shirazu.ac.ir.
Reza
R
Yousefi
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D061986:MCF-7 Cells; D008968:Molecular Conformation; D010793:Phthalazines / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010793:Phthalazines; D010984:Platinum; D004247:DNA; C043388:phthalazine; D053148:Caspase 3
Anticancer drugs; Apoptosis; Cancer cells; DNA damage; Platinum complexes