Synthesis and Biological Evaluation of Militarin Derivatives

밀리타린 유도체의 합성 및 생리활성 평가

  • Che, Haiyan (College of Pharmacy, Kangwon National University) ;
  • Yoon, Deok Hyo (College of Natural Sciences of Kangwon National University) ;
  • Kim, Tae Woong (College of Natural Sciences of Kangwon National University) ;
  • Sung, Gi-Ho (Rural Development Administration) ;
  • Park, Haeil (College of Pharmacy, Kangwon National University)
  • Received : 2012.10.04
  • Accepted : 2012.12.07
  • Published : 2012.12.31

Abstract

Militarin was isolated from Cordyceps militaris, a caterpillar-grown traditional medicinal mushroom and reported to possess anticancer activities against several tumor cells. A number of militarin derivatives bearing different numbers of ethylene glycol unit were synthesized and evaluated for their biological activities related with anticancer and antiinflammatory effects. Among militarin derivatives tested, the compounds 2 and 5 exhibited anticancer and antiinflammatory activities.

Keywords

References

  1. Cho, M. A., Lee, D. S., Kim, M. J., Sung, J. M. and Ham, S. S. : Antimutagenecity and cytotoxicity of cordycepin isolated from Cordyceps militaris. Food Sci. Biotechnol. 12, 472 (2003).
  2. Choi, S. B., Park, C. H., Choi, M. K., Jun, D. W. and Park, S. M. : Improvement of insulin resistance and insulin secretion by water extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% pancreatectomized rats. Biosci. Biotechnol. Biochem. 68, 2257 (2004). https://doi.org/10.1271/bbb.68.2257
  3. Yoo, H. S., Shin, J. W., Cho, J. H., Son, C. G., Lee, Y. W., Park, S. Y. and Cho, C. K. : Effect of Cordyceps militaris extract on angiogenesis and tumor growth. Acta Pharmacol. Sin. 25, 657 (2004).
  4. Yun, Y. H., Han, S. H., Lee, S. J., Ko, S. K., Lee, C. K., Ha, N. J. and Kim, K. J. : Anti-diabetic effects of CCCA, CMESS and cordycepin from Cordyceps militaris and the immune responses in streptozotocin-induced diabetic mice. Nat. Prod. Sci. 9, 291 (2003).
  5. Kim, H. G., Shrestha, B., Lim, S. Y., Yoon, D. H., Chang, W. C., Shin, D. J., Han, S. K., Park, S. M., Park, J. H., Park, H. I., Sung, J. M., Jang, Y. S., Chung, N. S., Hwang, K. C. and Kim, T. W. : Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-${\kappa}B$ through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur. J. Pharmacol. 545, 192 (2006). https://doi.org/10.1016/j.ejphar.2006.06.047
  6. Chang, W., Lim, S., Song, H., Song, B. W., Kim, H. J., Cha, M. J., Sung, J. M., Kim, T. W. and Hwang, K. C. : Cordycepin inhibits vascular smooth muscle cell proliferation. Eur. J. Pharmacol. 597, 64 (2008). https://doi.org/10.1016/j.ejphar.2008.08.030
  7. 김태웅, 주식회사머쉬텍, 성재모 : 밀리타리스 동충하초로부터 분 리된 항암활성이 있는 신물질과 그 제조방법 및 용도. 대한민국 등록특허 10-0538311 (2005).
  8. Che, H., Truong, N. T., Yoon, D. H., Kim, T. W., Sung, K. H. and Park, H. : Development of an efficient synthetic method for a anticancer substance isolated from insect-flower. Yakhak Hoeji 56, 71 (2012).
  9. Gutierrez-Rodriguez, M., Garcia-Lopez, M. T. and Herranz, R. : Improved synthesis of a [4.4]-spirolactam $\beta$-turn mimetic as surrogate of the didemnin side chain dipeptide Pro-N-Me-DLeu. Tetrahedron 60, 5177 (2004). https://doi.org/10.1016/j.tet.2004.04.052
  10. Alesso, S. M., Yu, Z., Pears, D., Worthington, P. A., Luke, R. W. A. and Bradley, M. : Improving resins for solid phase synthesis: incorporation of 1-[2-(2-methoxyethoxy)ethoxy]-4- vinylbenzene. Tetrahedron 59, 7163 (2003). https://doi.org/10.1016/S0040-4020(03)01100-1