Open AccessImpact of Mitochondrial Targeting Antibiotics on Mitochondrial Function and Proliferation of Cancer Cells
Author(s) -
Edward J Cochrane,
James Hulit,
Franz P Lagasse,
Tanguy Lechertier,
Brett Stevenson,
Corina Tudor,
Diana Trebicka,
Tim Sparey,
Andrew J. Ratcliffe
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00632
Subject(s) - mitochondrion , doxycycline , mitochondrial ribosome , antibiotics , cancer cell , mitochondrial dna , ribosomal rna , bioenergetics , chemistry , biology , microbiology and biotechnology , biochemistry , cancer , ribosome , gene , rna , genetics
Some marketed antibiotics can cause mitochondria dysfunction via inhibition of the mitochondrial translation process. There is great interest in exploiting such effects within a cancer setting. To enhance accumulation of antibiotics within the mitochondria of cancer cells, and therefore delivery of a greater potency payload, a mitochondrial targeting group in the form of a triphenylphosphonium (TPP) cation was appended via an alkyl chain length consisting of 7 to 11 carbons to the ribosomal antibiotics azithromycin and doxycycline. Using MDA-MB-231 cells, the effects of each subseries on mitochondrial translation, mitochondrial bioenergetics, and cell viability are described.