Development of mitochondria-targeted derivatives of resveratrol.
To target natural polyphenols to the subcellular site where their redox properties might be exploited at best, that is, mitochondria, we have synthesised new proof-of-principle derivatives by linking resveratrol (3,4',5-trihydroxy-trans-stilbene) to the membrane-permeable lipophilic triphenylphosphonium cation. The new compounds, (4-triphenylphosphoniumbutyl)-4'-O-resveratrol iodide and its bis-acetylated derivative, the latter intended to provide transient protection against metabolic conjugation, accumulate into energized mitochondria as expected and are cytotoxic for fast-growing but not for slower-growing cells. They provide a powerful potential tool to intervene on mitochondrial and cellular redox processes of pathophysiological relevance.
Biasutto
Lucia
L
Department of Chemical Sciences, Università di Padova, via Marzolo 1, 35131 Padova, Italy.
Mattarei
Andrea
A
Marotta
Ester
E
Bradaschia
Alice
A
Sassi
Nicola
N
Garbisa
Spiridione
S
Zoratti
Mario
M
Paradisi
Cristina
C
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D002412:Cations; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005419:Flavonoids / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry; D059808:Polyphenols; D051381:Rats; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D012995:Solubility; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D000975:Antioxidants; D002412:Cations; D005419:Flavonoids; D016877:Oxidants; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014867:Water; D000077185:Resveratrol