Synthesis of hybrid phosphorated indenoquinolines and biological evaluation as topoisomerase I inhibitors and antiproliferative agents

Bioorg Med Chem Lett. 2022 Feb 1:57:128517. doi: 10.1016/j.bmcl.2021.128517. Epub 2021 Dec 21.

Abstract

This work describes the first synthesis of diethyl 6,6a,7,11b-tetrahydro-5H-indeno[2,1-c]quinolinylphosphonates 5, diethyl 7H-indeno[2,1-c]quinolinylphosphonates 6 and diethyl 7-oxo-7H-indeno[2,1-c]quinolinylphosphonates 7, which were prepared in good to high overall yields. The synthetic route involves a multicomponent reaction of 2-phosphonateaniline, aldehydes and indene as olefin and allows the selective generation of three stereogenic centres in a short, efficient and reliable manner. The selective dehydrogenation of 1,2,3,4-tetrahydroindenoquinolines leads to the formation of corresponding indenoquinolines, and subsequent oxidation of methylene group of the indenoquinolines allows the access to indenoquinolinones.

Keywords: Antiproliferative effect; Enzyme inhibition; Indenoquinolinyl phosphonates; Topoisomerase I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Indenes / chemical synthesis
  • Indenes / pharmacology*
  • Phosphorous Acids / chemical synthesis
  • Phosphorous Acids / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / pharmacology*
  • Stereoisomerism
  • Topoisomerase I Inhibitors / chemical synthesis
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents
  • Indenes
  • Phosphorous Acids
  • Quinolines
  • Topoisomerase I Inhibitors