Synthesis of fluorinated triphenylphosphonium analogs that improve cancer cell selectivity and in vivo detection

STAR Protoc. 2023 Sep 15;4(3):102437. doi: 10.1016/j.xpro.2023.102437. Epub 2023 Aug 7.

Abstract

Triphenylphosphonium (TPP+) compounds like mito-metformin (MMe) target cancer cells by exploiting their hyperpolarized mitochondrial membrane potential. Here, we present a protocol for synthesizing TPP+ analogs with selectivity for mammalian cancer cells, reduced toxicity, and quantifiability using fluorine-19 nuclear magnetic resonance (19F-NMR). We describe steps for treating mammalian cells with mitochondria-targeted compounds, treating and preparing mouse tissue with these compounds, and 19F-NMR detection of MMe analogs in cells and tissue. TPP+-conjugated metformin analogs include para-methoxy (pMeO-MMe) and para-trifluoromethyl MMe (pCF3-MMe) and meta-trifluoromethyl MMe (mCF3-MMe).

Keywords: Cancer; Chemistry; Metabolism; Model Organisms; NMR.

MeSH terms

  • Animals
  • Endrin / analogs & derivatives*
  • Mammals
  • Metformin* / metabolism
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Mice
  • Mitochondria / metabolism
  • Neoplasms* / diagnostic imaging
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / metabolism
  • Organophosphorus Compounds / pharmacology

Substances

  • triphenylphosphonium
  • MME
  • Organophosphorus Compounds
  • Metformin
  • Endrin