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The Pharmaceutical Society of Korea (대한약학회)
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A Cholesterol Biosynthesis Inhibitor from Rhizopus oryzae

  • Kim, Hyun-Jung (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Yim, Soon-Ho (Jeonnam Biotechnology Center for Biaindustry) ;
  • Lee, Ik-Soo (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
  • Published : 2004.06.01
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Abstract

A bile acid derivative, methyl chalate （1）, was isolated from EtOAc extract of the fungus Rhizopus oryzae as a cholesterol biosynthesis inhibitor. It showed moderate inhibitory activity on cholesterol biosynthesis in human Chang liver cells. Compound 1 exhibited inhibitory effect on the later step of cholesterol biosynthesis, indicating that its action mode is different from that of statins that act on the HMG-CoA reductase.

Keywords

References

  1. Abe, I., Tomesch, J. C., Wattanasin, S., and Prestwich, G. D., Inhibitors of squalene biosynthesis and metabolism. Nat. Prod. Rep., 11, 279-302 (1994) https://doi.org/10.1039/np9941100279
  2. Alam, N., Bae, B. H., Hong, J., lee, C.-O., Shin, B. A., Im, K. S., and Jung, J. H., Additional bioactive Lyso-PAF congeners from the sponge Spirastrella abata. J. Nat. Prod., 64, 533-535 (2001) https://doi.org/10.1021/np0005210
  3. Biller, S. A., Sofia, M. J., Abt, J. W., DeLange, B., Dickson, J. K. Jr., Forster, C., Gordon, E. M., Harrity, T, Magnin, D. R., Marretta, J., Rich, L. C., and Ciosek, C. P. Jr., Potent, rationally designed inhibitors of squalene synthase, In Nes, W. D., Parish, E. J. and Trzaskos, J. M. (Eds.). Regulation of isoprenoid metabolism. American Chemical Society, Washington DC, pp.65-80(1992)
  4. Brown, M. S. and Goldstein, J. L., Heart attacks: gone with the century? Science, 272, 629 (1996) https://doi.org/10.1126/science.272.5262.629
  5. Dias, J. R., Gao, H., and Kolehmainen, E., $^1^3{C}$ nuclear magnetic resonance data of bile acid derivatives. Spectrochim. Acta, Part，56, 53-77 (2000) https://doi.org/10.1016/S1386-1425(99)00135-3
  6. Endo, A. and Hasumi, K., HMG-CoA reductase inhibitors. Nat. Prod. Rep., 10, 541-550 (1993) https://doi.org/10.1039/np9931000541
  7. Gebhardt, R., Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids, 28, 613-619 (1993) https://doi.org/10.1007/BF02536055
  8. Gebhardt, R., Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts. J. Pharmacol. Exp. Ther.，286, 1122-1128 (1998)
  9. Gerst, N., Duriatti, A., Schuber, F., Taton, M., Benveniste, P., and Rahier, A., Potent inhibition of cholesterol biosynthesis in 3T3 fibroblasts by N-[(1,5,9)-trimethyldecyl]-4${\alpha}$, 10-dimethyl-8- aza-trans-decal-3${\beta}$-ol, a new 2,3-oxidosqualene cyclase inhibitor. Biochem. Pharmacol., 37, 1955-1964 (1988) https://doi.org/10.1016/0006-2952(88)90542-4
  10. Goto, J., Sano, Y, Chikai, T., and Nambara, T., Synthesis of disulfates of unconjugated and conjugated bile acids. Chem. Pharm. Bull., 35, 4562-4567 (1987) https://doi.org/10.1248/cpb.35.4562
  11. Grabley, S., Granzer, E., Hutter, K., Ludwig, D., Mayer, M., Thiericke, R., Till, G., Wink, J., Philipps, S., and Zeeck, A., Secondary metabolites by chemical screening. 8. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium. I. Strain description, fermentation, isolation and properties. J. Antibiotics, 45, 56-65 (1992) https://doi.org/10.7164/antibiotics.45.56
  12. Kim, H. J., Yim, S.-H., Sung, C. K., Jung, J. H., Shin, B. A., and Lee, I.-S., A new ergostane-type cholesterol biosynthesis inhibitor isolated from Hormoconis resinae. Tetrahedron Lett., 44, 7159-7162 (2003) https://doi.org/10.1016/S0040-4039(03)01808-2
  13. Lipid Research Clinics Program, The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. J. Am. Med. Assoc., 251, 351-364 (1984a) https://doi.org/10.1001/jama.251.3.351
  14. Lipid Research Clinics Program, The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction of coronary heart diease to cholesterol lowering. J. Am. Med. Assoc., 251, 365-374 (1984b) https://doi.org/10.1001/jama.251.3.365
  15. Metherall, J. E., Waugh, K., and Li, H., Progesterone inhibits cholesterol biosynthesis in cultured cells. J. Biol. Chem., 271, 2627-2633 (1996) https://doi.org/10.1074/jbc.271.5.2627
  16. Robbers , J. E., Speedie, M. K., and Tyler, V. E., Pharmacognosy and Pharmacobiotechnology, Williams & Wilkins , Baltimore (1996)
  17. Shepherd , J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., MacFarlane, P. W., McKillop, J. H., and Packard, C. J., Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N. Engl. J. Med., 333, 1301-1307(1995) https://doi.org/10.1056/NEJM199511163332001
  18. Shin, B. A., Kim, Y. R., Lee, I.-S., Sung, C. K., Hong, J., Sim, C. J., Im, K. S., and Jung, J. H., Lyso-PAFanalogues and Iysophosphatidylcholines from the marine sponge Spirastrella abata as inhibitors of cholesterol biosynthesis. J. Nat. Prod., 62, 1554-1557 (1999) https://doi.org/10.1021/np990303a
  19. Trenin, A. S.,Terekhova, L. P., Tolstykh, I. V., Zenkova, V. A., Fedorova, G. B., and Katrukha, G. S., Screening of microbial secondary metabolites inhibiting cholesterol biosynthesis with the use of hepatoblastoma G2 cell culture. Antibiot. Khimioter., 48, 3-8 (2003)