title: Structure-activity relationships of yessotoxins in cultured cells.
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. Under our experimental conditions, the EC(50) 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 EC(50) for this compound was 0.62 nM. The EC(50) values we measured for 45-hydroxyhomoyessotoxin and carboxyyessotoxin were about 9.4 and 26 nM, respectively, whereas the EC(50) 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 EC(50)'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.
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via G. Campi 287, I-41100 Modena, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrari
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ciminiello
authors.forename: Carmen
authors.initials: C
authors.lastname: Dell'Aversano
authors.forename: Martino
authors.initials: M
authors.lastname: Forino
authors.forename: Claudia
authors.initials: C
authors.lastname: Malaguti
authors.forename: Aurelia
authors.initials: A
authors.lastname: Tubaro
authors.forename: Roberto
authors.initials: R
authors.lastname: Poletti
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yasumoto
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fattorusso
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossini
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects*; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000633:toxicity*; D008978:Mollusk Venoms / Q000737:chemistry* / Q000633:toxicity*; D035964:Oxocins / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
chemical_list: D004988:Ethers, Cyclic; D008978:Mollusk Venoms; D035964:Oxocins; C066632:yessotoxin