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A Mitochondriotropic Derivative of Quercetin: A Strategy to Increase the Effectiveness of Polyphenols
Author(s) -
Mattarei Andrea,
Biasutto Lucia,
Marotta Ester,
De Marchi Umberto,
Sassi Nicola,
Garbisa Spiridione,
Zoratti Mario,
Paradisi Cristina
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800162
Subject(s) - mitochondrion , quercetin , chemistry , polyphenol , biochemistry , organelle , mitochondrial permeability transition pore , reactive oxygen species , redox , programmed cell death , apoptosis , antioxidant , organic chemistry
Mitochondria‐targeted compounds are needed to act on a variety of processes that take place in these subcellular organelles and that have great pathophysiological relevance. In particular, redox‐active molecules that are capable of homing in on mitochondria provide a tool to intervene on a major cellular source of reactive oxygen species and on the processes they induce, notably the mitochondrial permeability transition and cell death. We have linked the 3‐OH of quercetin (3,3′,4′,5,7‐pentahydroxy flavone), a model polyphenol, and the triphenylphosphonium moiety, a membrane‐permeant cationic group, to produce proof‐of‐principle mitochondriotropic quercetin derivatives. The remaining hydroxyls were sometimes acetylated to hinder metabolism and improve solubility. The new compounds accumulate in mitochondria in a transmembrane potential‐driven process and are only slowly metabolised by cultured human colon cells. They inhibit mitochondrial ATPase activity much as quercetin does, and are toxic for fast‐growing cells.