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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Hetero-multinuclear ruthenium(III)/platinum(II) complexes that potentially exhibit both antimetastatic and
Craig M Anderson1, Isabelle R Taylor, Michael F Tibbetts
1Department of Chemistry, Bard College, 30 Campus Rd, Annandale-on-Hudson, New York 12504, United States. canderso@bard.edu
Abstract:
Hetero-multinuclear, platinum/ruthenium species were synthesized and tested for their effect on the motility of A549 (nonsmall cell lung) and MDA-MB-231 (breast) cancer cells and for their ability to inhibit DNA mobility using gel electrophoresis. It was found that the Ru(2)Pt trinuclear species [Na(2)]{[Ru(III)Cl(4)(DMSO-S)(-μ-pyz)](2)Pt(II)Cl(2)}, AH197, was much more efficient at inhibiting cell motility than [C(3)N(2)H(5)][Ru(III)Cl(4)(DMSO-S)(C(3)N(2)H(4))], NAMI-A, while the dinuclear RuPt species [K][Ru(III)Cl(4)(DMSO-S)(-μ-pyz)Pt(II)(DMSO-S)Cl(2)], IT127, was slightly better than NAMI-A. However, the dinuclear species retarded the electrophoretic mobility of DNA greater than both the trinuclear complex and cisplatin. The metal complexes and their respective BSA protein/metal adducts were studied by X-ray absorption spectroscopy. The spectra led to the conclusion that BSA donor atoms have substituted for the chloride ligands and perhaps the DMSO ligands.
Insights
New platinum/ruthenium metal complexes show promise in cancer research. The trinuclear complex AH197 effectively inhibited cancer cell motility, while dinuclear complexes impacted DNA mobility more than cisplatin.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Biochemistry
Background:
- Platinum and ruthenium compounds are extensively studied for their anticancer properties.
- Metal complexes offer diverse coordination environments and reactivity for therapeutic applications.
Purpose of the Study:
- To synthesize and evaluate novel hetero-multinuclear platinum/ruthenium complexes.
- To assess the impact of these complexes on cancer cell motility and DNA mobility.
- To investigate the interaction of these complexes with biological molecules like BSA.
Main Methods:
- Synthesis of Ru(2)Pt trinuclear (AH197) and RuPt dinuclear (IT127) complexes.
- Evaluation of cell motility inhibition in A549 (non-small cell lung) and MDA-MB-231 (breast) cancer cell lines.
- Assessment of DNA mobility inhibition using gel electrophoresis.
- X-ray absorption spectroscopy (XAS) to study metal-protein adducts.
Main Results:
- The trinuclear Ru(2)Pt complex AH197 demonstrated superior inhibition of cancer cell motility compared to NAMI-A.
- The dinuclear RuPt complex IT127 showed slightly better cell motility inhibition than NAMI-A.
- Dinuclear RuPt species exhibited greater retardation of DNA electrophoretic mobility than the trinuclear complex and cisplatin.
- XAS studies indicated substitution of chloride and possibly DMSO ligands by BSA donor atoms.
Conclusions:
- Hetero-multinuclear platinum/ruthenium complexes exhibit differential effects on cancer cell motility and DNA mobility.
- AH197 is a potent inhibitor of cancer cell motility.
- Dinuclear RuPt complexes possess significant DNA-binding or DNA-interacting capabilities.
- BSA interactions involve ligand substitution, suggesting potential mechanisms for in vivo activity.
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