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

Biol Pharm Bull. 1999 Sep;22(9):1010-2. doi: 10.1248/bpb.22.1010.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Hydroxamic Acids / pharmacology
  • Isoquinolines / pharmacology*
  • Isoquinolines / therapeutic use
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Melanoma, Experimental
  • Mice
  • Neoplasm Invasiveness / prevention & control
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Isoquinolines
  • N-(2,6-diethylphenyl)homophthalimide
  • N-(2,6-dimethylphenyl)homophthalimide
  • Aminopeptidases
  • Leucine
  • ubenimex
  • actinonin