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. Under our experimental conditions, the EC50 of YTX, the reference compound, was 0.55 nM. The introduction of a methylene unit adjacent to one of the sulfate groups, as is the case with the homoyessotoxin molecule, did not appear to greatly affect the potency of the analogue, as the measured 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. A comparison of our findings with available information regarding the potency of YTX and its analogues in other experimental systems shows that the EC50'S we measured for the different compounds are up to 200-fold lower and vary in a wider concentration range. We speculate that YTX effects could involve two separate receptorial systems.
Structure-activity relationships of yessotoxins in cultured cells / Ferrari, Sara; P., Ciminiello; C., Dell'Aversano; M., Forino; C., Malaguti; A., Tubaro; R., Poletti; T., Yasumoto; E., Fattorusso; Rossini, Gian Paolo. - In: CHEMICAL RESEARCH IN TOXICOLOGY. - ISSN 0893-228X. - STAMPA. - 17:(2004), pp. 1251-1257.