The structure-activity relationship of yessotoxins (YTX) has been probed by measuring the potency of several YTX analogues to cause the accumulation of a 100 kDa MW fragment of E-cadherin in MCF-7 breast cancer cells. The EC50 of YTX, the reference compound, was 0.55 nM. The introduction of a methylene unit adjacent to one of the sulfate groups (homoyessotoxin) did not appear to greatly affect the potency of the analogue, as the EC50 for this compound was 0.62 nM. The EC50 values we measured for 45-hydroxyhomoyessotoxin and carboxyyessotoxin were about 9.4 and 26 nM, respectively, whereas the EC50 of noroxoyessotoxin, lacking most of the C(9) chain, was about 50 nM. Thus, significant differences in the potencies of YTX analogues were found when structural changes involved the C(9) terminal chain of these compounds, leading to the conclusion that this portion of the molecule is essential for the activity of YTX in MCF-7 cells.

Structure-activity relationships of yessotoxins in cultured cells

TUBARO, AURELIA;
2004-01-01

Abstract

The structure-activity relationship of yessotoxins (YTX) has been probed by measuring the potency of several YTX analogues to cause the accumulation of a 100 kDa MW fragment of E-cadherin in MCF-7 breast cancer cells. The EC50 of YTX, the reference compound, was 0.55 nM. The introduction of a methylene unit adjacent to one of the sulfate groups (homoyessotoxin) did not appear to greatly affect the potency of the analogue, as the EC50 for this compound was 0.62 nM. The EC50 values we measured for 45-hydroxyhomoyessotoxin and carboxyyessotoxin were about 9.4 and 26 nM, respectively, whereas the EC50 of noroxoyessotoxin, lacking most of the C(9) chain, was about 50 nM. Thus, significant differences in the potencies of YTX analogues were found when structural changes involved the C(9) terminal chain of these compounds, leading to the conclusion that this portion of the molecule is essential for the activity of YTX in MCF-7 cells.
2004
http://pubs.acs.org/doi/pdf/10.1021/tx030054x
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/1701611
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