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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 IC50 values 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.

journal_name

ACS Med Chem Lett

journal_title

ACS medicinal chemistry letters

authors

Smithrud DB,Wang X,Tarapore P,Ho SM

doi

10.1021/ml3003204

subject

Has Abstract

pub_date

2013-01-10 00:00:00

pages

27-31

issue

1

issn

1948-5875

journal_volume

4

pub_type

杂志文章

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