title: Ca2+Selective Host Rotaxane Is Highly Toxic Against Prostate Cancer Cells.
abstract: New therapies are needed to eradicate androgen resistant, prostate cancer. Prostate cancer usually metastasizes to bone where the concentration of calcium is high, making Ca2+a promising toxin. Ionophores can deliver metal cations into cells, but are currently too toxic for human use. We synthesized a new rotaxane (CEHR2) that contains a benzyl 15-crown-5 ether as a blocking group to efficiently bind Ca2+. CEHR2 transfers Ca2+from an aqueous solution into CHCl3to greater extent than alkali metal cations and Mg2+. It also transfers Ca2+to a greater extent than CEHR1, which is a rotaxane with an 18-crown-6 ether as a blocking group. CEHR2 was more toxic against the prostate cancer cell lines PC-3, 22Rv1, and C4-2 than CEHR1. This project demonstrates that crown ether rotaxanes can be designed to bind a targeted metal cation, and this selective cation association can result in enhanced toxicity.
authors.affiliation: Contribution from the Department of Chemistry, University of Cincinnati , Cincinnati, Ohio 45221, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Smithrud
authors.affiliation: Contribution from the Department of Chemistry, University of Cincinnati , Cincinnati, Ohio 45221, United States.
authors.forename: Lucas
authors.initials: L
authors.lastname: Powers
authors.affiliation: Contribution from the Department of Chemistry, University of Cincinnati , Cincinnati, Ohio 45221, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lunn
authors.affiliation: Contribution from the Department of Chemistry, University of Cincinnati , Cincinnati, Ohio 45221, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Abernathy
authors.affiliation: Contribution from the Department of Chemistry, University of Cincinnati , Cincinnati, Ohio 45221, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Peschka
authors.affiliation: Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, Center for Environmental Genetics, and Cancer Institute, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States; Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, Center for Environmental Genetics, and Cancer Institute, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States; Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, Center for Environmental Genetics, and Cancer Institute, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States; Cincinnati Veterans Affairs Medical Center, 3200 Vine Street, Cincinnati, Ohio 45220, United States.
authors.forename: Shuk-Mei
authors.initials: SM
authors.lastname: Ho
authors.affiliation: Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, Center for Environmental Genetics, and Cancer Institute, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States; Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, Center for Environmental Genetics, and Cancer Institute, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States; Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, Center for Environmental Genetics, and Cancer Institute, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States.
authors.forename: Pheruza
authors.initials: P
authors.lastname: Tarapore
keywords: Prostate cancer; calcium; crown ethers; rotaxanes