Design, Synthesis, and Action of Antiatherogenic Antioxidants

  • Osamu Cynshi
  • Kunio Tamura
  • Etsuo Niki
Part of the Methods in Molecular Biology book series (MIMB, volume 610)


Ample evidence supports the critical role of oxidized low-density lipoprotein (ox-LDL) in initiation and progression of atherosclerosis. Oxidation of LDL is a complex process involving several steps (processes) of reactions such as initiation and propagation. Both proteins and lipids in LDL undergo free radical-mediated oxidations leading to the formation of ox-LDL that plays a pivotal role in atherosclerosis. Antioxidants of various types (both aqueous and lipophilic) either arrest or retard the oxidation of LDL at various steps of the oxidation process (e.g., initiation or propagation). Certain lipophilic antioxidants act as the chain-terminating antioxidants leading to the inhibition of LDL oxidation. The current chapter describes the designing and efficacy of two novel lipophilic antioxidants (benzofuranol, BO-653 and aniline, BO-313) in inhibiting the LDL oxidation and atherogenesis in experimental animal model. Furthermore, the characteristics of an effective antioxidant to inhibit LDL oxidation and atherogenesis which dictates the designing of the antioxidant drug and its mechanism(s) of antiatherogenic action are discussed.

Key words

Antioxidant low-density lipoprotein (LDL) LDL oxidation thiobarbituric acid reactive substances (TBARS) gel permeation chromatography (GPC) Watanabe heritable hyperlipidemic (WHHL) rabbit atherosclerosis, 2,2’–azobis 2-amidinopropane (AAPH), lipoxygenase, N-(3,7,11,15-tetramethylhexadecyl)-3,4,5-trimethoxyaniline (BO-313) 4,6-Di-tert-butyl-2,3-dihydro-2,2-dipentyl-5-benzofuranol (BO-653) 



The authors thank Drs. T. Kodama at Tokyo University and T. Kita at Kyoto University for providing excellent advice on atherosclerosis in animal models. We also thank Drs. Y. Kawabe, Y. Kato, T. Suzuki, Y. Takashima, M. Takeda, H. Kaise, M. Kim, J. Aono, and Y. Ohba for their collaboration on this project in Chugai Pharmaceutical Co., Ltd. and Ms Ford Frances for her editorial assistance.


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Osamu Cynshi
    • 1
  • Kunio Tamura
    • 1
  • Etsuo Niki
    • 2
  1. 1.Fuji-gotemba Research LaboratoriesChugai Pharmaceutical Co., Ltd.ShizuokaJapan
  2. 2.Human Stress Signal Research Center, National Institute of Advanced Industrial Science and TechnologyOsakaJapan

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