(-)-Phenylahistin arrests cells in mitosis by inhibiting tubulin polymerization

(-)-Phenylahistin, a fungal diketopiperazine metabolite composed of phenyla lanine and isoprenylated dehydrohistidine, arrested cells in mitosis and in hibited the proliferation of A549 cells. The microtubule network in A549 ce lls was disrupted by (-)-phenylahistin, which also inhibited the polymeriza tion of both microtubule protein from bovine brain and phosphocellulose-pur ified tubulin in vitro. Competitive binding studies indicated that (-)-phen ylahistin interacted with the colchicine binding site on tubulin but not wi th the vinblastine binding site.