Design, synthesis, and evaluation of an α-tocopherol analogue as a mitochondrial antioxidant.
An efficient synthesis has provided access to a novel α-tocopherol analogue (2), as well as its trifluoroacetate salt and acetate ester. An annulation reaction was used to establish the pyridinol core structure and a Stille coupling reaction was employed for conjugation with the tocopherol side chain. This analogue was shown to suppress the levels of reactive oxygen species in cultured cells, and to quench peroxidation of mitochondrial membranes.
Lu
Jun
J
Center for BioEnergetics, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Khdour
Omar M
OM
Armstrong
Jeffrey S
JS
Hecht
Sidney M
SM
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
C555725:(3-hydroxy-3,7,11,15-tetramethylhexadecyl)-1,6-dimethyl-2,3-dihydro-1H-pyrrolo(2,3-b)pyridin-5-ol; D000975:Antioxidants; D004224:Diterpenes; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D017382:Reactive Oxygen Species; C527741:pyrrolopyrimidine; D024502:alpha-Tocopherol