Inhibition of ABCG2-mediated drug efflux by naphthopyrones from marine crinoids

Bioorg Med Chem Lett. 2010 Jul 1;20(13):3848-50. doi: 10.1016/j.bmcl.2010.05.057. Epub 2010 May 21.

Abstract

Five new naphthopyrones (1-5) along with the known compounds TMC-256A1, 5,8-dihydroxy-6-methoxy-2-propyl-4H-naphtho[2,3-b]pyran-4-one, TMC-256C1, comaparvin, 6-methoxycomaparvin, and 6-methoxycomaparvin 5-methyl ether (6-11) were isolated from crinoids of the family Comasteridae. All compounds were tested for their ability to inhibit the multidrug transporter ABCG2, which plays a role in drug resistance. Six of the seven angular naphthopyrones showed moderate activity with <60% inhibition of ABCG2-mediated transport as compared to the positive control fumitremorgin C. None of the linear naphthopyrones inhibited ABCG2-mediated efflux.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / antagonists & inhibitors*
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Echinodermata / chemistry*
  • Humans
  • Molecular Conformation
  • Naphthalenes / chemistry
  • Naphthalenes / isolation & purification
  • Naphthalenes / pharmacology*
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Pyrones / chemistry
  • Pyrones / isolation & purification
  • Pyrones / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Naphthalenes
  • Neoplasm Proteins
  • Pyrones