Synthesis, structures and biomolecular interactions of new silver(I) 5,5-diethylbarbiturate complexes of monophosphines targeting Gram-positive bacteria and breast cancer cells
No Thumbnail Available
Date
2017-05-24
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Royal Soc Chemistry
Abstract
A series of new silver(I) 5,5-diethylbarbiturate (barb) complexes with the formulas [Ag-2(mu-barb)(2)(PPh3)(2)] (1), [Ag(barb)(PPh2Cy)] (2), [Ag(barb)(PPhCy2)] (3) and [Ag(barb)(PCy3)] (4) (PPh3 = triphenylphosphine, PPh2Cy = diphenylcyclohexylphosphine, PPhCy2 = dicyclohexylphenylphosphine and PCy3 = tricyclo-hexylphosphine) were synthesized and fully characterized by elemental analysis, IR, NMR, ESI-MS and X-ray crystallography. All the complexes display a significant affinity towards DNA with a groove binding mode and also strongly bind to BSA via hydrophobic interactions. Lipophilicity increases from 1 to 4 with an increasing number of Cy groups in the phosphine ligands. Screening of the in vitro antimicrobial activity of 1-4 against the strains of Gram-negative (S. typhimurium ATCC 14028, E. coli ATCC 25922 and O157:H7) and Gram-positive (L. garvieae 40456, S. aureus ATCC 25923, and ATCC 33591) bacteria demonstrated that all the complexes exhibit very high activity and specific selectivity against the Gram-positive bacteria, compared to AgNO3 and silver sulfadiazine. Furthermore, the growth inhibitory effects of 1-4 on four human cancer cell lines (MCF-7, PC-3, A549 and HT-29) showed that 4 has a potent cytotoxic activity against MCF-7 cells, significantly higher than cisplatin and carboplatin. The effects of the complexes on the inhibition of the cells are closely related to their lipophilicity as well as DNA/protein binding. The induction of apoptosis of MCF-7 cells treated with 4 was probed through Hoechst 33342 staining, Annexin V positivity and caspase 3/7 activity. In addition, increased ROS levels in the presence of 4 are most likely responsible for damage to both mitochondria and genomic DNA.
Description
Keywords
Chemistry, Heterocyclic carbene complexes, Bovine serum-albumin, Crystal-structures, Dna-binding, 2,2'-dipyridylamine synthesis, Antimicrobial activity, Antibacterial agents, Antioxidant activity, Phosphorus ligands, Molecular docking, Bacteria, Binding energy, Bins, Cell culture, Cell death, Cells, Complexation, Crystallography, Cytology, Cytotoxicity, Diseases; E, Escherichia coli, Hydrophobicity, Ligands, Phosphorus compounds, Platinum compounds, Self assembly, Silver, X ray crystallography, Synthesis (chemical), 5 ,5-diethylbarbiturate, Anti-microbial activity, Biomolecular interactions, Gram-positive bacterium, Groove binding modes, Hydrophobic interactions, Silver sulfadiazines, Triphenyl phosphines
Citation
Yılmaz, V. T. vd. (2017). ''Synthesis, structures and biomolecular interactions of new silver(I) 5,5-diethylbarbiturate complexes of monophosphines targeting Gram-positive bacteria and breast cancer cells''. Dalton Transactions. 46(25), 8110-8124.