Potent homophthalimide-type inhibitors of B16F10/L5 mouse melanoma cell invasion.

Recently, we developed a series of novel and potent aminopeptidase inhibitors with a homophthalimide skeleton. Among them, N-(2,6-diethylphenyl)homophthalimide (PIQ-22) possesses a specific aminopeptidase-inhibiting activity more potent than that of bestatin or actinonin, as assayed in terms of hydrolysis of L-alanine 4-methylcoumaryl-7-amide (Ala-AMC) by human acute lymphoblastic leukemia MOLT-4 cells. We show here that PIQ-22 and its 2,6-dimethylphenyl derivative (PIQ-11) are more potent inhibitors of tumor cell invasion than bestatin and actinonin in a Matrigel assay using mouse melanoma B16F10/L5 cells.