Novel non-trimethoxylphenyl piperlongumine derivatives selectively kill cancer cells

Bioorg Med Chem Lett. 2017 Jun 1;27(11):2308-2312. doi: 10.1016/j.bmcl.2017.04.035. Epub 2017 Apr 13.

Abstract

Piperlongumine (PL) is a natural alkaloid with broad biological activities. Twelve analogues have been designed and synthesized with non-substituted benzyl rings or heterocycles in this work. Most of the compounds showed better anticancer activities than the parent PL without apparent toxicity in normal cells. Elevation of cellular ROS levels was one of the main anticancer mechanisms of these compounds. Cell apoptosis and cell cycle arrest for the best compound ZM90 were evaluated and similar mechanism of action with PL was demonstrated. The SAR was also characterized, providing worthy directions for further optimization of PL compounds.

Keywords: Anticancer; Drug design; Natural product; Piperlongumine; Structure-activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Dioxolanes / chemistry
  • Dioxolanes / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Dioxolanes
  • Reactive Oxygen Species
  • piperlongumine