Design, Synthesis and Biological Evaluation of Jahanyne Analogs as Cell Cycle Arrest Inducers

Mar Drugs. 2020 Mar 23;18(3):176. doi: 10.3390/md18030176.

Abstract

Jahanyne, a lipopeptide with a unique terminal alkynyl and OEP (2-(1-oxo-ethyl)-pyrrolidine) moiety, exhibits anticancer activity. We synthesized jahanyne and analogs modified at the OEP moiety, employing an α-fluoromethyl ketone (FMK) strategy. Preliminary bioassays indicated that compound 1b (FMK-jahanyne) exhibited decreased activities to varying degrees against most of the cancer cells tested, whereas the introduction of a fluorine atom to the α-position of a hydroxyl group (2b) enhanced activities against all lung cancer cells. Moreover, jahanyne and 2b could induce G0/G1 cell cycle arrest in a concentration-dependent manner.

Keywords: G0/G1 phase arrest; jahanyne; lipopeptide; α-fluoromethyl ketone.

MeSH terms

  • Apoptosis / drug effects
  • Aquatic Organisms / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyanobacteria / chemistry
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Lipopeptides / chemical synthesis
  • Lipopeptides / pharmacology*
  • Lipopeptides / therapeutic use
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Lipopeptides
  • jahanyne