Evidence for the Rapid Conversion of Stephacidin B into the Electrophilic Monomer Avrainvillamide in Cell Culture

Abstract
We report that the dimeric alkaloid stephacidin B (1) and the monomeric alkaloid avrainvillamide (2) function equivalently within experimental error to inhibit the growth of four different cultured human cancer cell lines. We also show that the proportion of the monomer greatly outweighs that of the dimer in the medium of incubation, and that the half-life for the transformation of 1 to 2 is short relative to the half-life of cell division. Finally, using a monomer-based affinity reagent, we provide evidence that the monomer (2) interacts with intracellular thiol-containing proteins, likely by covalent modification.