title: Design, synthesis, and action of antiatherogenic antioxidants.
abstract: 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.
authors.affiliation: Fuji-gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Cynshi
authors.forename: Kunio
authors.initials: K
authors.lastname: Tamura
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D003300:Copper / Q000737:chemistry; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000814:Aniline Compounds; D000975:Antioxidants; D001572:Benzofurans; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D003300:Copper; C023650:aniline