Synthesis and evaluation of hapalosin and analogs as MDR-reversing agents

Bioorg Med Chem Lett. 1999 Jun 7;9(11):1541-6. doi: 10.1016/s0960-894x(99)00243-7.

Abstract

The marine natural product hapalosin and 22 analogs, which incorporated systematic substituent deletions or variations, were prepared. These compounds were evaluated in a cell-based assay for both MDR-reversing activity and general cytotoxicity. Some substituent modifications resulted in lower cytotoxicities, but most structural changes were either detrimental to or did not seriously alter the MDR-reversing activity.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Depsipeptides*
  • Drug Resistance, Multiple*
  • Humans
  • Inhibitory Concentration 50
  • Lactams / chemical synthesis*
  • Lactones / chemical synthesis*
  • Mice
  • Models, Chemical
  • Recombinant Proteins / metabolism
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Depsipeptides
  • Lactams
  • Lactones
  • Recombinant Proteins
  • hapalosin