Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities

Bioorg Med Chem Lett. 2017 Oct 15;27(20):4682-4686. doi: 10.1016/j.bmcl.2017.09.013. Epub 2017 Sep 8.

Abstract

Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5μM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36.2μM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.

Keywords: 2-Cyanoacryloyl; Anti-proliferative activity; Michael acceptor; NF-κB; Pregnenolone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyanoacrylates / chemistry*
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Humans
  • MCF-7 Cells
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Pregnenolone / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cyanoacrylates
  • NF-kappa B
  • Pregnenolone