Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Cytotoxic Polyene Antibiotics from Myxococcus stipitatus JW111

Myxococcus stipitatus JW111이 생산하는 Polyene계 항암활성물질

  • Ahn, Jong-Woong (Bio-Organic Science Division, Korea Research Institute of Chemical Technology)
  • 안종웅 (한국화학연구원 화학물질부)
  • Published : 2002.05.31
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Abstract

Phenalamides $A_1{\sim}A_3$ were reisolated as cytotoxic substances from culture broth of Myxococcus stipitatus JW111. The producing strain was isolated from the marine sediment collected off the shore of Geomun Island, Korea. The active principles were extracted from cell mass with acetone and successively purified by silica gel column chromatography, Sephadex LH-20 column chromatography, and finally recycling prep. HPLC. These compounds demonstrated significant cytotoxicity against certain human cancer cells, having $IC_50$ values ranging from 0.23 to 0.50 ${\mu}g/ml$. Moreover, they also inhibited the growth of adriamycin-resistant HCT/ADM human cancer cell line as well as its parent sensitive cell line.

점액세균의 대사산물을 대상으로 새로운 항암활성물질을 탐색하는 과정에서 해양퇴적물에서 분리한 균주 JW111의 균체 추출액이 인체유래의 각종 암세포에 대해 강한 활성을 나타냄을 발견하고, 먼저 생산균주인 JW111이 Myxococcus stipitatus임을 확인한 후 그 대사산물을 분리, 정제하여 구조결정한 결과, Phenalamide $A_1$, $A_2E, $A_3$임을 밝혔다. 이들은 공시된 감수성 암세포에 대해 모두 우수한 활성을 나타내었으며, $IC_50$의 값은 $0.23{\sim}0.50{\mu}g/ml$이었다. 또한 이들은 Adriamycin의 내성 세포주에 대해서도 감수성 세포주와 동일한 활성을 나타내어 내성을 나타내지 않음이 확인되었다.

Keywords

References

  1. Reichenbach, H. and Hoefle, G. (1999) In Drue discovery from nature. Spinger, Berlin, Heidelberg, New York. pp. 149-179
  2. Reichenbach, H. and Hoefle, G. (1993) hi Myxobacteria II.American Society for Microbiology, Washington. pp. 347-397
  3. Kunze, B., Reichenbach, H., Augustiniak, H. and Hoefle, G (1982) Isolation and identification of althiomycin from C. fuscus. J. Antibiotics 35, 635-636. https://doi.org/10.7164/antibiotics.35.635
  4. Rosenberg, E., Fyilovirch, S., Carmeli, S. and Kashman, Y. (1982) Chemical properties of M. xanthus antibiotic TA. J. Antibiotics 35, 788-793 https://doi.org/10.7164/antibiotics.35.788
  5. Trowitzsch, W., Wray, V, Gerth, K. and Hoefle, G. (1982) Structure of myxovirescm A, a new macrocyclic antibiodc from gliding bacteiia. J. Chem. Soc. Chem. Commun. 1982, 1340-1342
  6. Onishi, N., Izaki, K. and Takahashi, H. (1984) A macrocydic antibiotic M-230B produced by M. xanthus. J. Antibiotics 37, 13-19 https://doi.org/10.7164/antibiotics.37.13
  7. Cowden, C. J. and Paterson, I. (1997) Cancer drugs better than taxol? Nature 387, 238-239 https://doi.org/10.1038/387238a0
  8. Wessjohann, L, (1997) Epothilones: Promising natural products with taxol-like activity. Angew. Chem. Int. Ed. Engl. 36, 715-71 https://doi.org/10.1002/anie.199707151
  9. Sasse, R, Steinmetz, H., Heil, J., Hoefle, G. and Reichenbach, H. (2000) Tubulysins, new cytostatic peptides from Myxobacteha acting on microtubli. J. Antibiotics 53, 879-885 https://doi.org/10.7164/antibiotics.53.879
  10. Kunze, B., Jansen, R., Sasse, R, Hoefle, G. and Reichenbach, H. (1998) Apicularens A and B, new cytostatic macrolides from Chondmmyces sp. J. Antibiotics 51, 1075-1080 https://doi.org/10.7164/antibiotics.51.1075
  11. Ahn, J. -W., Woo, S. -H., Lee, C. -0., Cho, K. -Y. and Kim, B. -S. (1999) KR025, a new cytotoxic compound from Myxococcus fulvus. J. Nat. Prod. 62, 495-496 https://doi.org/10.1021/np9804233
  12. Reichenbach, H. (1996) Biologically active secondary metabolites from microorganism. GBF Scientific Annual Report, GBF, Braunschweig, Germany
  13. Iizuka, T, Jojima, Y, Fudou, R and Yamanaka S. (1998) Isolation of myxobacteha from the marine environment. FEMS Microbiot. Lett. 169, 317-322 https://doi.org/10.1111/j.1574-6968.1998.tb13335.x
  14. Fudou, R., lizuka, T. and Yamanaka S. (2001) Haliangicin, a novel antifungal metabolite produced by a marine myxobactehum. J. Antibiotics 54, 149-152 https://doi.org/10.7164/antibiotics.54.149
  15. Reichenbach, H. and Dworkin, M. (1992) In The Myxobacteria: the Prokaryotes (2nd ed.) Springer Verlag, New York. pp. 3416-3426
  16. Irschik, H., Jansen, R., Hoefle, G., Gerth, K. and Reichenbach, H. (1985) The corallopyronins, new inhibitors of bacterial RNA synthesis from myxobacteha. J. Antibiotics 38, 145-152 https://doi.org/10.7164/antibiotics.38.145
  17. Yamanaka, S., Kawaguchi, A. and Komagata, K. (1987)Isolation and identification of myxobacteria. J. Gen. Appl. Microbiol. 33, 247-265 https://doi.org/10.2323/jgam.33.247
  18. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J., Bokesch, H., Kenny, S. and Boyd, MR. (1990) New colorimethc cytotoxicity assay for anticancer drug screening. J. Nat. Cancer Inst. 82, 1107-1112 https://doi.org/10.1093/jnci/82.13.1107
  19. Trowitzsch-Kienast, W., Forche, E., Wray, V., Reichenbach, H., Jurkiewicz, E., Hunsmann, G. and Hoefle, G. (1992) Phenalamide, neue HIV-1 inhibitoren aus M. stipitatus Mx s40. Liebigs Ann. Chem. 1992, 659-664
  20. JurIdewicz, E., Jansen, R., Kunze, B., rowitzsch-Kienast, W., Porche, E., Reichenbach, H., Hoefle, G. and Hunsmann, G. (1992) Three new potent HIV-l inhibitors from myxobacteha. Antivirat Chemistry & Chemotherapy 3, 189-193 https://doi.org/10.1177/095632029200300401