Aureobasidins as new inhibitors of P-glycoprotein in multidrug resistant tumor cells

J Antibiot (Tokyo). 1998 Mar;51(3):353-8. doi: 10.7164/antibiotics.51.353.

Abstract

Cyclic depsipeptide antibiotic aureobasidin A (AbA) and its analogs were tested for the inhibitory activity of P-glycoprotein in multidrug resistant cancer cells as well as for the antifungal activity. Some analogs with lower antifungal activity than AbA showed higher inhibition of P-glycoproteins indicating difference of the structure-activity relationships between the two activities. Among AbA analogs tested, [D-beta-hydroxy-methylvalyl9]-AbA newly prepared by chemical synthesis, which had much lower antifungal activity than AbA, showed 10-fold higher inhibitory activity of P-glycoprotein than AbA.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP-Binding Cassette Transporters / biosynthesis
  • Antifungal Agents / pharmacology*
  • Depsipeptides*
  • Humans
  • Multidrug Resistance-Associated Proteins
  • Peptides, Cyclic / pharmacology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Vincristine / pharmacokinetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antifungal Agents
  • Depsipeptides
  • Multidrug Resistance-Associated Proteins
  • Peptides, Cyclic
  • aureobasidin A
  • Vincristine