FPTase Inhibition Effect of Protostanes from Alismatis Rhizoma and Derivatives from Alisol B 23-acetate

택사 (Alismatis Rhizoma)에서 분리한 Protostane계 화합물과 그 유도체의 FPTase 억제활성

  • Received : 2011.06.17
  • Accepted : 2011.08.11
  • Published : 2011.09.30

Abstract

The purpose of this research is to study of inhibitory activity of protostane type triterpens against farnesyl-protein transferase (FPTase). The ingredients of Alismatis Rhizoma, alisol B 23-acetate, C 23-acetate, alisols B and A 24-acetate, and thirteen synthetic analogues from alisol B 23-acetate exhibited inhibition activity against FPTase by scintillation proximity assay method. As a result, alisol C 23-acetate, one of the constituents of Alismatis Rhizoma, the synthetic analogues carboxylated and hydroxylated on branch chain of protostane exhibited a significant inhibitory activity. However, the compounds significantly lowered the inhibitory activity, when there is no 3 position keto on protostane skeletone.

Keywords

References

  1. 생약학교재편찬위원회, 생약학 (2006) 1:283, 동명사, 서울.
  2. 정보섭, 신민교, 도해향약(생약)대사전 (1990) 1:269, 영림사, 서울.
  3. Murata, T., Shinohara, M. and Miyamoto, M. (1970) Biological- active triterpens of Alismatis Rhizoma. I. Isolation of the alisol. Chem. Pharm. Bull. 18: 1347-1353. https://doi.org/10.1248/cpb.18.1347
  4. Murata, T., Shinohara, M. and Miyamoto, M. (1970) Biological active triterpenes of Alismatis Rhizoma. I. Isolation of the alisol. Chem. Pharm. Bull. 18: 1369-1384. https://doi.org/10.1248/cpb.18.1369
  5. Fukuyama, Y., Geng, P., Wang, R., Yamada, Y. and Nakagawa, K. (1988) 11-deoxy alisol C and alisol D: New protostane- type triterpenoids from Alisma plantago-aquatica. Planta Med. 54: 445-447. https://doi.org/10.1055/s-2006-962495
  6. Yoshikawa, M., Hatakeyma, S., Tanaka, N., Matsuoka, T., Yamahara, J. and Murakami, N. (1993) Crude drugs from aquatic plants. II. On the constituents of the rhizome of A. orientale juzep. Chem. Pharm. Bull. 41: 2109-2112. https://doi.org/10.1248/cpb.41.2109
  7. Zeng, L., Pen, X. and Ru, Y. (1995) Alizexol A, a novel protostane type of triterpen from Alisma oriental (SAM) juzep, Chin. Chim. Lett. 6: 675-678.
  8. Yamada, S., Yamaguchi, T., Naito T. and Hashimoto, K. (1995) New alisol, and cerebral function-improving agent containing alisol compound as active ingredient. Japanes Patent. JP07173188.
  9. Kimura, H., Ogata, T. and Sato, Y. (1992) Therapeutic agent of hepatic disease containing alismol-relating compound as active ingredient. Japans Patent. JP04077420.
  10. Lee, J. H., Kang, K. S. and Ahn, B. J. (1986) Cytotoxic screening of oriental drugs and forklores against L1210 cells. K. J. Pharmacon. 17: 286-291.
  11. Pomplino, D. L., Rands, E., Schaber, M. D., Mosser, S. D., Anthony, N. J. and Gibbs, J. B. (1992) Steady-state kinetic mechanism of Ras farnesyl-protein transferase. Biochem. 31: 3800-3807. https://doi.org/10.1021/bi00130a010
  12. Lowy, D. R. and Willumsen, B. M. (1993) Function and regulation of RAS. Ann Rev. Biochem. 62: 851-891. https://doi.org/10.1146/annurev.bi.62.070193.004223
  13. Miura, S., Hasumi, K. and Endo, A. (1993) Inhibition of protein prenylation by patulin. FEBS Letter 318: 88-90. https://doi.org/10.1016/0014-5793(93)81334-V
  14. Singh, S. B., Jones, E. T., Goetz, M. A., Bills, G. F. and Nallin, M. (1994) Fusidinol: A novel inhibitor of ras farnesylprotein transferase from fussidium griseum. Tetradron Lett. 35: 4693-4696. https://doi.org/10.1016/S0040-4039(00)76943-7
  15. Van der Pyl, D., Cans P., Debernard, J. J., Herman, F., Lelievre, Y., Tahraoui, L., Vuilhorgne, M. and Leboul, J. (1995) RPR113228, a novel farnesyl-protein transferase inhibitor produced by Chrysosporium lobatum. J. Antibiot. 48: 736-737. https://doi.org/10.7164/antibiotics.48.736
  16. Singh, S. B., Zink, D. L., Bills, G. F., Jenkins, R. G., Silverman, K. C. and Lingham R. B. (1995) Cylindrol A: a Novel inhibitor of ras farnesyl-protein transferase from Cylindrocarpon lucidum. Tetrahedron Lett. 36: 4935-4938. https://doi.org/10.1016/00404-0399(50)0896K-
  17. David, W. P., Robert, W. P., Raymond, L. B., Raymond, Y., Mohindar, S. P., Mahesh, P. W., Robert, B. and Stephen J. C. (1995) SCH 58450, a novel farnesyl protein transferase inhibitor possessing a 6a, 12a:7,12-diepoxybenz[a]anthracene ring system. Tetrahedron Lett. 36: 6995-6998. https://doi.org/10.1016/0040-4039(95)01589-A
  18. Jayasuriya, H., Ball, R. G., Zink, D. L., Smith, J. L., Goetz, M. A., Jenkins, R. G., Nallin-Omstead, M., Silverman, K. C., Bills, G. F. and Lingham, R. B. (1995) Barceloneic acid A, a new farnesyl-protein transferase inhibitor from a Phoma species. J. Nat. Prod. 58: 986-991. https://doi.org/10.1021/np50121a002
  19. Silverman, K. C., Cascales, C., Genilloud, O., Sigmund, J. M., Gartner, S. E., Koch, G. E., Gagliardi M. M., Heimbuch, B. K., Nallin-Omstead , M., Sanchez, M., Diez, M. T., Martin, I., Garrity, G. M., Hirsch, C. F., Gibbs, J. B., Singh, S. B. and Lingham, R. B. (1995) Actinoplanic acids A and B as novel inhibitors of farnesyl-protein transferase. Appl. Microbiol. Biotech., 43: 610-616. https://doi.org/10.1007/BF00164762
  20. Lee, S. M., Kho, Y. H., Min, B. S., Kim, J. H., Na, M. K., Kang, S. J., Maeng, H. Y. and Bae, K. H. (2001) Cytotoxic triterpenoides from Alismatis Rhizoma. Arch. Pharm. Res. 24: 524-526. https://doi.org/10.1007/BF02975158
  21. Lee, S. M., Min, B. S. and Bae, K. H. (2002) Chemical modification of alisol B 23-acetate and their cytotoxic activity. Arch. Pharm. Res. 25: 608-612. https://doi.org/10.1007/BF02976929