Hypolipidemic and Antioxidant Activity of the Novel Acyl-CoA:Cholesterol Acyltransferase (ACAT) Inhibitor KY-455 in Rabbits and Hamsters

Arzneimittel-Forschung/Drug Research

Volumn 54, Issue 2, 2004, Pages 102-108

  Nakamura, Shohei ^a   Kamiya, Shoji ^a   Shirahase, Hiroaki ^a   Kanda, Mamoru ^a   Yoshimi, Akihisa ^a   Tarumi, Tadatsugu ^a   Kurahashi, Kazuyoshi ^b  

^a Research Laboratories   (Japan)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

Acyl CoA:cholesterol acyltransferase inhibitor; CAS 178469 71 1; KY 455, antioxidant activity, hamster, hypolipidemic effect, rabbit; N (4,6 Dimethyl 1 pentylindolin 7 yl) 2,2 dimethylpropanamide

Indexed keywords

CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CHOLESTEROL ESTER; KY 455; LOW DENSITY LIPOPROTEIN CHOLESTEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTICLE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL DIET; CONTROLLED STUDY; DRUG INHIBITION; ENZYME ACTIVITY; EXPERIMENTAL MODEL; HAMSTER; HYPOLIPEMIA; IC 50; LIPID PEROXIDATION; LIPOPROTEIN BLOOD LEVEL; LIVER CELL; MACROPHAGE; MALE; NONHUMAN; RABBIT; SINGLE DRUG DOSE;

EID: 1342284384     PISSN: 00044172     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0031-1296943     Document Type: Article

References (14)

1. Sliskovic, D. R., White, A. D., Therapeutic potential of ACAT inhibitors as lipid lowering and anti-atherosclerotic agents. Trends Pharmacol. Sci. 12, 194 (1991)
2. Fukushima, H., Nakatani, H., Cholesterol-lowering effects of DL-N-(α-methylbenzyl)-linoleamide and its optically active isomers in cholesterol-fed animals. J. Atheroscler. Res. 9, 65 (1969)
3. Natori, K., Okazaki, Y., Nakajima, T. et al., Mechanism of the inhibition of cholesterol absorption by DL-melinamide: Inhibition of cholesterol esterification. Japan. J. Pharmacol. 42, 517 (1986)
4. Matsuda, K., ACAT inhibitors as antiatherosclerotic agents: Compounds and mechanisms. Med. Res. Rev. 14, 271 (1994)
5. Roth, B. D., ACAT inhibitors: evolution from cholesterol-absorption inhibitors to antiatherosclerotic agents. Drug Discov. Today 3, 19 (1998)
6. Lee, H. T., Sliskovic, D. R., Picard, J. A. et al., Inhibitors of acyl-CoA:cholesterol O-acyl transferase (ACAT) as hypocholesterolemic Agents. CI-1011: an acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets. J. Med. Chem. 39, 5031 (1996)
7. Jackson, R. L., Ku, G., Thomas, C. E., Antioxidants: a biological defense mechanism for the prevention of atherosclerosis. Med. Res. Rev. 13, 161 (1993)
8. Holvoet, P., Collen, D., Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis 137, S33 (1998)
9. Nagano, Y., Nakamura, T., Matsuzawa, Y. et al., Probucol and atherosclerosis in the Watanabe heritable hyperlipidemic rabbit - long-term antiatherogenic effect and effects on established plaques. Atherosclerosis 92, 131 (1992)
10. Kamiya, S., Shirahase, H., Yoshimi, A. et al., Bioavailable acyl-CoA:choelsterol acyltransferase inhibitor with anti-peroxidative activity: synthesis and biological activity of novel indolinyl amide and urea derivatives. Chem. Pharm. Bull. 48, 817 (2000)
11. Field, F. J., Mathur, S., β-Sitosterol: esterification by intestinal acylcoenzyme A:cholesterol acyltransferase (ACAT) and its effect on cholesterol esterification. J. Lipid Res. 24, 409 (1983)
12. Heider, J. G., Pickens, C. E., Kelly, L. A., Role of acyl CoA: cholesterol acyltransferase in cholesterol absorption and its inhibition by 57-118 in the rabbit. J. Lipid Res. 24, 1127 (1983)
13. Breugnot, C., Iliou, J. P., Privat, S. et al., In vitro and ex vivo inhibition of the modification of low-density lipoprotein by indapamide. J. Cardiovasc. Pharmacol. 20, 340 (1992)
14. Fosch, J., Lees, M., Sloane-Stanley, G. H. S., A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226, 497 (1957)