A green multicomponent synthesis of tocopherol analogues with antiproliferative activities

Eur J Med Chem. 2018 Jan 1:143:1888-1902. doi: 10.1016/j.ejmech.2017.11.003. Epub 2017 Nov 3.

Abstract

A one-pot efficient, practical and eco-friendly synthesis of tocopherol analogues has been developed using water or solvent free conditions via Passerini and Ugi multicomponent reactions. These reactions can be optimized using microwave irradiation or ultrasound as the energy source. Accordingly, a small library of 30 compounds was prepared for biological tests. The evaluation of the antiproliferative activity in the human solid tumor cell lines A549 (lung), HBL-100 (breast), HeLa (cervix), SW1573 (lung), T-47D (breast), and WiDr (colon) provided lead compounds with GI50 values between 1 and 5 μM. A structure-activity relationship is also discussed. One of the studied compounds comes up as a future candidate for the development of potent tocopherol-mimetic therapeutic agents for cancer.

Keywords: Antiproliferative; Green conditions; Microwaves; Multicomponent reactions; Ultrasound; Water.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Tocopherols / chemical synthesis
  • Tocopherols / chemistry
  • Tocopherols / pharmacology*

Substances

  • Antineoplastic Agents
  • Tocopherols