Fluorinated triphenylphosphonium analogs improve cell selectivity and in vivo detection of mito-metformin.

ABSTRACT: Triphenylphosphonium (TPP⁺) conjugated compounds selectively target cancer cells by exploiting their hyperpolarized mitochondrial membrane potential. To date, studies have focused on modifying either the linker or the cargo of TPP⁺-conjugated compounds. Here, we investigated the biological effects of direct modification to TPP⁺ to improve the efficacy and detection of mito-metformin (MMe), a TPP⁺-conjugated probe we have shown to have promising preclinical efficacy against solid cancer cells. We designed, synthesized, and tested trifluoromethyl and methoxy MMe analogs (pCF₃-MMe, mCF₃-MMe, and pMeO-MMe) against multiple distinct human cancer cells. pCF₃-MMe showed enhanced selectivity to

SUBMITTER: AbuEid M 

PROVIDER: S-EPMC9768319 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature