Targeted therapies have become the focus of much of the cancer therapy research conducted in the United States. While these therapies have made vast improvements in the treatment of cancer, their results have been somewhat disappointing due to acquired resistances, high cost, and limited populations of susceptible patients. As a result, targeted therapeutics are often combined with other targeted therapeutics or chemotherapies. Compounds which target more than one cancer related pathway are rare, but have the potential to synergize multiple components of therapeutic cocktails. Natural products, as opposed to targeted therapies, typically interact with multiple cellular targets simultaneously, making them a potential source of synergistic cancer treatments. In this study, a rare natural product, deacetylnemorone, was shown to inhibit cell growth in a broad spectrum of cancer cell lines, selectively induce cell death in melanoma cells, and inhibit angiogenesis and invasion. Combined, these results demonstrate that deacetylnemorone affects multiple cancer-related targets associated with tumor growth, drug resistance, and metastasis. Thus, the multi-targeting natural product, deacetylnemorone, has the potential to enhance the efficacy of current cancer treatments as well as reduce commonly acquired treatment resistance.
Targeted therapies have changed the treatment of cancer, giving new hope to many patients in recent years. The shortcomings of targeted therapies including acquired resistance, limited susceptible patients, high cost, and high toxicities, have led to the necessity of combining these therapies with other targeted or chemotherapeutic treatments. Natural products are uniquely capable of synergizing with targeted and non-targeted anticancer regimens due to their ability to affect multiple cellular pathways simultaneously. Compounds which provide an additive effect to the often combined immune therapies and cytotoxic chemotherapies, are exceedingly rare. These compounds would however provide a strengthening bridge between the two treatment modalities, increasing their effectiveness and improving patient prognoses. In this study, 7-epi-clusianone was investigated for its anticancer properties. While previous studies have suggested clusianone and its conformational isomers, including 7-epi-clusianone, are chemotherapeutic, few cancer types have been demonstrated to exhibit sensitivity to these compounds and little is known about the mechanism. In this study, 7-epi-clusianone was shown to inhibit the growth of 60 cancer cell types and induce significant cell death in 25 cancer cell lines, while simultaneously modulating the immune system, inhibiting angiogenesis, and inhibiting cancer cell invasion, making it a promising lead compound for cancer drug discovery.
Having worked on several approaches to CO2 capture over the past decade, we have studied a great number of physical and chemical solvents as well as polymer and composite membranes. Initially, most of these materials were based upon ionic liquids (ILs), however due to challenges encountered in applying ILs to meet the demanding requirements in CO2 separation processes, there is a need to reconsider what role (if any) ILs might play in CO2 capture technologies. Ultimately, more promising and robust materials will not come from ILs themselves, but from retrosynthetic analysis and a reconsideration of which structural variables and properties are (and are not) important. The hybridization of the constituent parts into entirely new, yet seemingly familiar substances, can yield greatly improved properties and economics. This manuscript highlights recent work from our group based on lessons learned from ILs that have spurred the development of new amine solvents and polymer materials to better address the demanding process conditions and requirements of CO2 capture and related separations.
1-Vinylimidazole has been extensively utilized by the polymer science community, due to its high reactivity for free radical polymerization and the variety of uses for both neutral polyvinylimidazole and cationic polyvinylimidazolium forms. While much rarer, 4-vinylimidazoles and 2-vinylimidazoles are less synthetically accessible. In comparison to conventional methods for the synthesis of vinylimidazole derivatives from energy-intensive reaction conditions utilizing hazardous, gaseous precursors, herein we demonstrate a simple and versatile two-step method applied to the synthesis of seven 1-vinylimidazoles with different substituents as well as an initial demonstration of a facile method to synthesize the rare compound 1-methyl-2-vinylimidazole. The process relies upon the synthesis of N-hydroxyethylimidazole precursors via a ring-opening reaction from substituted imidazoles with ethylene carbonate, a 'green' substance formed from CO 2 and ethylene oxide. For the synthesis of 1-methyl-2-vinylimidazole, the hydroxyethylimidazole intermediate is conveniently formed from 1,2-dimethylimidazole and paraformaldehyde. These hydroxyethylimidazoles are subsequently dehydrated to the corresponding 1-or 2-vinylimidazole forms using a base-catalyzed reactive distillation. The optimization of process conditions is discussed, and properties of the vinylimidazole derivatives were computationally studied using density functional theory calculations. This work reveals scalable synthetic methods for previously inaccessible vinylimidazole compounds which can enable the design of new polymers.
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