Ca2+ Selective Host Rotaxane Is Highly Toxic Against Prostate Cancer Cells

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• 作者：David B. SmithrudLucas Powers ; Jennifer Lunn ; Scott Abernathy ; Michael Peschka ; Shuk-mei Ho ; Pheruza Tarapore
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：February 9, 2017
• 年：2017
• 卷：8
• 期：2
• 页码：163-167
• 全文大小：371K
• ISSN：1948-5875

文摘

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 CHCl₃ to 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.