Isofistularin

Neither 79 nor 80 are detected in the intact tissue of the sponge implying that substrates and enzymes for the conversion are stored in different cellular compartments or different cell types. When isofistularin-3 (76) is the substrate, 77 is detected as a second cleavage product of this reaction. This wound-activated bioconversion is paralleled by a marked increase of biological activity of the products 79 and 80 compared to the isoxazolines. In feeding assays the aqueous... 

The above described rationale of SAR can be exemplified by the bioactivities of the bromotyrosine derivatives, aeroplysinin-1 and dienone, as well as their complicated molecular substrates aerophobin-1 and isofistularin-3, isolated from the Mediterranean sponge, Aplysina aerophoba. Aeroplysinin-1 and dienone exhibit pronounced biological activity whereas aerophobin-1 and isofistularin-3 were always inactive when tested in equimolar concentrations [23]. Aeroplysinin-1 and dienone are antibiotically active against a broad spectrum of marine bacteria such as Vibrio, Micrococcus, and Alteromonas species [24] and are also cytotoxic to Ehrlich ascites tumour cells and HeLa tumour cells in the microculture tetrazolium (MTT) and clonogenic assays [25]. In these assays, it has been demonstrated that the free radical transformation of aeroplysinin-1 and dienone to its semiquinone structures are responsible for the cytotoxicity [25], Aeroplysinin-1 and dienone are the pharmacophores of aerophobin-1 and isofistularin-3. 

Most of the bis-spirocyclohexadienyhsoxazoline type of bromotyrosine derivatives tested exhibited moderate cytotoxicity against different cancer cell lines. These include fistularin-3 (79) (68), 11-oxoaerothionin (72) (64), ll-ep/-fistularin-3 (81) (70), 11-oxofistularin (82) (72), isofistularin-3 (80) (72), and ll-deoxyfistularin-3 (86) (73). 11-Oxoaerothionin (72) is the most potent agent and showed pronounced selective cytotoxic activity toward the human colon HCT cell line at a limited concentration range of 0.01-0.1 pg/mL (64). 

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