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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 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.

SUBMITTER: Smithrud DB

PROVIDER: S-EPMC5304289 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Smithrud David B DB Powers Lucas L Lunn Jennifer J Abernathy Scott S Peschka Michael M Ho Shuk-Mei SM Tarapore Pheruza P

ACS medicinal chemistry letters 20170104 2

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 CHCl< ...[more]

PMID: 28197305

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