Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents

Zachary S. Gardner, Tanner J. Schumacher, Conor T. Ronayne, Greeshma P. Kumpati, Michael J. Williams, Akira Yoshimura, Hithardha Palle, Chinnadurai Mani, Jon Rumbley, Venkatram R. Mereddy

Research output: Contribution to journalArticlepeer-review

Abstract

Several phosphonium derivatives have been synthesized from Baylis-Hillman (BH) reaction derived allyl bromides and aryl phosphines as mitochondria targeting anticancer agents. In vitro cell proliferation inhibition studies on various solid tumor cell lines indicate that most of the compounds exhibit IC50 values in µM concentrations. Further studies reveal that β-substituted BH bromide derived phosphonium derivatives enhance the biological activity to low µM IC50 values. In vitro metabolic studies show that the lead candidate compound 16 inhibits the production of mitochondrial ATP, increases the proton leak within the mitochondrial membrane and abolishes the spare respiratory capacity in a concentration dependent manner.

Original languageEnglish (US)
Article number128136
JournalBioorganic and Medicinal Chemistry Letters
Volume45
DOIs
StatePublished - Aug 1 2021

Bibliographical note

Funding Information:
We thank the Department of Chemistry and Biochemistry, University of Minnesota Duluth, College of Pharmacy and Integrated Biosciences, University of Minnesota, Randy Shaver Cancer Research and Community Fund, Whiteside Clinical Research Institute for their financial support.

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

  • Anticancer agent
  • Baylis-Hillman reaction
  • MTT and SRB assay
  • MitoStress test
  • Phosphonium derivatives

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