Structural revision of kynapcin-12 by total synthesis, and inhibitory activities against prolyl oligopeptidase and cancer cells

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3373-6. doi: 10.1016/j.bmcl.2014.05.091. Epub 2014 Jun 4.

Abstract

Kynapcin-12 is a prolyl oligopeptidase (POP) inhibitor isolated from Polyozellus multiplex, and its structure was assigned as 1 having a p-hydroquinone moiety by spectroscopic analyses and chemical means. This Letter describes the total syntheses of the proposed structure 1 for kynapcin-12 and 2',3'-diacetoxy-1,5',6',4″-tetrahydroxy-p-terphenyl 2 isolated from Boletopsis grisea, revising the structure of kynapcin-12 to the latter. These syntheses involved double Suzuki-Miyaura coupling, CAN oxidation, and LTA oxidation as key steps. The inhibitory activities of synthetic compounds against POP and cancer cells were also evaluated.

Keywords: Kynapcin-12; Prolyl oligopeptidase inhibitor; p-Terphenyl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • HL-60 Cells
  • Humans
  • Molecular Structure
  • Prolyl Oligopeptidases
  • Serine Endopeptidases / metabolism*
  • Structure-Activity Relationship
  • Terphenyl Compounds / chemistry
  • Terphenyl Compounds / isolation & purification
  • Terphenyl Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Terphenyl Compounds
  • kynapcin 12
  • Serine Endopeptidases
  • PREPL protein, human
  • Prolyl Oligopeptidases