title: Crown Ether Host-Rotaxanes as Cytotoxic Agents.
abstract: Highly toxic bacterial ionophores are commonly used in veterinary medicine, but their therapeutic index is too narrow for human usage. With the goal of developing ionophores with a broader therapeutic index, we constructed highly derivatized synthetic ionophores. The toxicities of crown ether host-rotaxanes (CEHR's) against the SKOV-3 cell line were measured. The effect of Mg2+or Ca2+on toxicity was explored because changes in the intracellular concentration of these cations can cause cell death through apoptosis. We found Boc-CEHR is highly toxic and Arg-CEHR is slightly less toxic with IC50values of 0.5 μM and 6 μM, respectively, in standard growth medium. Increasing the concentration of Ca2+resulted in greater toxicity of the CEHRs, whereas increasing the concentration of Mg2+was less effective on reducing IC50. Cell death occurs mainly through apoptosis. Although preliminary, these results suggest that the CEHRs deliver Ca2+and perhaps Mg2+into cells inducing apoptosis.
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 452212.
authors.forename: David B
authors.initials: DB
authors.lastname: Smithrud
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Pheruza
authors.initials: P
authors.lastname: Tarapore
authors.forename: Shuk-Mei
authors.initials: SM
authors.lastname: Ho
keywords: Apoptosis; Calcium; Crown Ethers; Magnesium; Rotaxanes
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