Rhodanine-3-acetic Acid Derivatives as Inhibitors of Fungal Protein Mannosyl Transferase 1 (PMT1)

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3975-8. doi: 10.1016/j.bmcl.2004.05.050.

Abstract

The first inhibitors of fungal protein: mannosyl transferase 1 (PMT1) are described. They are based upon rhodanine-3-acetic acid and several compounds have been identified, for example, 5-[[3-(1-phenylethoxy)-4-(2-phenylethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid (5a), which inhibit Candida albicans PMT1 with IC(50)s in the range 0.2-0.5 microM. Members of the series are effective in inducing changes in morphology of C. albicans in vitro that have previously been associated with loss of the transferase activity. These compounds could serve as useful tools for studying the effects of protein O-mannosylation and its relevance in the search for novel antifungal agents.

MeSH terms

  • Candida albicans / drug effects
  • Candida albicans / enzymology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Fungi / drug effects
  • Fungi / enzymology
  • Mannosyltransferases / antagonists & inhibitors*
  • Microbial Sensitivity Tests
  • Rhodanine / analogs & derivatives*
  • Rhodanine / chemical synthesis
  • Rhodanine / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Rhodanine
  • Mannosyltransferases
  • protein O-mannosyltransferase