Reversal of fluconazole resistance in multidrug efflux-resistant fungi by the Dysidea arenaria sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate

J Nat Prod. 2003 Dec;66(12):1618-22. doi: 10.1021/np030317n.

Abstract

The sponge sterol 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate (ECTA) (1) is the first marine natural product to reverse fluconazole resistance mediated by a Candida albicans MDR efflux pump. The IC(50) of fluconazole is decreased from 300 to 8.5 microM (35-fold enhancement) when combined with 1(3.8 microM). A revised C-6 configuration of 1 is established.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphotericin B / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Candida albicans / drug effects
  • Cell Line, Tumor
  • Cholestenes / chemistry
  • Cholestenes / isolation & purification*
  • Cholestenes / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple
  • Drug Screening Assays, Antitumor
  • Fluconazole / pharmacokinetics*
  • Fluconazole / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Porifera / chemistry*

Substances

  • 9alpha,11alpha-epoxycholest-7-ene-3beta,5alpha,6alpha,19-tetrol 6-acetate
  • Antineoplastic Agents
  • Cholestenes
  • Amphotericin B
  • Fluconazole