Synthetic α-(aminomethyl)-γ-butyrolactones and their anti-pancreatic cancer activities

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6911-4. doi: 10.1016/j.bmcl.2013.09.065. Epub 2013 Sep 30.

Abstract

Aminated α-methylene-γ-butyrolactones, which are readily synthesized with facile control of the diastereoisomerism, provide an economical and commercially-viable alternative to the use of aminated natural products. These aminoloactones, which exhibit excellent activity against three pancreatic cancer cell lines when measured at 10 μM-Panc-1, MIA PaCa-2, and BxPC-3-and are comparable to or better than parthenolide and dimethylaminoparthenolide (DMAPT, LC-1). It has also been shown that there is an effect on the biological activity depending on the identity of the amine.

Keywords: Amination; Michael addition; Pancreatic cancer; Parthenolide; α-Methylene-γ-butyrolactones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Amination
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / toxicity
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • LC-1 compound
  • Sesquiterpenes
  • parthenolide
  • alpha-methylene gamma-butyrolactone
  • 4-Butyrolactone