The Synthesis, In Vitro and In Vivo Testing of Silver N-Heterocyclic Carbenes and Imidazolium Complexes
Full text release has been delayed at the author’s request until January 1, 2014.
Lung cancer remains a complex area of research to scientists due to its aggressive nature and high heterogeneity when compared to other cancers. There is a great demand to explore new chemotherapeutic options for the treatment of lung cancer. This demand comes not only from the standpoint of effective treatment, but also from the need to reduce the severe side effects of current treatments, which include; nausea, vomiting, hearing loss, and nerve damage. The antimicrobial properties of silver have been known for centuries, and silver has also been shown to have low toxicity in humans. Recently, our group has shown that silver also has anticancer properties against human ovarian, breast and lung cancer cell lines.
This dissertation describes the synthesis of a variety of Ag(I) compounds, and their in vitro and in vivo testing against a panel of cancerous cell lines. Chapter I of this dissertation discusses the background of medicinal N-heterocyclic carbene complexes including; silver, ruthenium, copper, and gold. Chapter II will discuss the synthesis and anticancer properties of fourteen 4,5-dichloroimidazole based di-N-heterocyclic carbene silver complexes acetate and silver benzoate complexes. The MTT assay was used to assess the in vitro activity of these di-silver carbene complexes against NCI-H460 non-small cell lung carcinoma cells. Chapter III is devoted to the in vitro anticancer properties of imidazolium cations and their silver N-heterocyclic carbene complexes based on methylnaphthalene ligands. These compounds were tested on NCI-H460 lung cancer cells, and both show anticancer properties. Chapter IV will focus on the in vivo activity of silver carbene complexes and silver carbene nanoparticles. Two major studies are described, one that demonstrates the low nebulized toxicity of PLGA-PEG-SCC23 in normal mice, and an orthotropic lung cancer model in nu/nu mice. This orthotropic model used transfected NCI-H460 cells and was treated by nebulization of PLGA-PEG-SCC23. Chapter V provides insight into a rabbit model of acute sinusitis, providing a means to determine if Ag(I) compounds are a potential treatment for such bacterial infections.
Document number: akron1353951003
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