Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum

J Nat Prod. 2002 Jul;65(7):979-85. doi: 10.1021/np0200616.

Abstract

Activity-guided fractionation of an ethanol extract of Lycopodium cernuum for Candida albicans secreted aspartic proteases (SAP) inhibition resulted in the identification of six new (1-6) and four known (7-10) serratene triterpenes, along with the known apigenin-4'-O-(2' ',6' '-di-O-p-coumaroyl)-beta-D-glucopyranoside (11). On the basis of spectroscopic analysis, the structures of 1-10 were established as 3beta,14alpha,15alpha,21beta,29-pentahydroxyserratane-24-oic acid (lycernuic acid C, 1), 3beta,14alpha,15alpha,21beta-tetrahydroxyserratane-24-oic acid (lycernuic acid D, 2), 3beta,14beta,21beta-trihydroxyserratane-24-oic acid (lycernuic acid E, 3), 3beta,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone A, 4), 3alpha,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone B, 5), 3alpha,21beta,24-trihydroxyserrat-14-en-16-one (lycernuic ketone C, 6), 3beta,21beta-dihydroxyserrat-14-en-24-oic acid (lycernuic acid A, 7), 3beta,21beta,29-trihydroxyserrat-14-en-24-oic acid (lycernuic acid B, 8), serrat-14-en-3beta,21beta-diol (9), and serrat-14-en-3beta,21alpha-diol (10). The 13C NMR data for the known compounds 7 and 8 are reported for the first time. Compounds 1 and 11 showed inhibitory effects against C. albicans secreted aspartic proteases (SAP) with IC50 of 20 and 8.5 microg/mL, respectively, while the other compounds were inactive.

Publication types

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

MeSH terms

  • Acetylation
  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Candida albicans / drug effects*
  • Chromatography, High Pressure Liquid
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Hydrolysis
  • Inhibitory Concentration 50
  • Lycopodiaceae / chemistry*
  • Molecular Conformation
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peru
  • Plants, Medicinal / chemistry*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / isolation & purification*
  • Protease Inhibitors / pharmacology
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification*
  • Triterpenes / pharmacology

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Protease Inhibitors
  • Triterpenes
  • Aspartic Acid Endopeptidases