Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and iNOS Inhibitory Activities of Thioflavones

  • Published : 2005.06.01
Download PDF
⟨ Previous Next ⟩

Abstract

A number of thioflavones has been synthesized and evaluated for their iNOS inhibitory activities. Thiowogonin (6) was obtained from naturally occurring chrysin in 5 steps. Other thioflavones were prepared from the corresponding flavones in a single step by the reaction with Lawesson's reagent. The biological activities of thioflavones were not enhanced by the functional group conversion from carbonyl to thiocarbonyl. Compounds 11 and 13 showed potent. NO inhibitory activity at high concentration (40 uM), leading to the possible development of novel neuroprotective agents based on wogonin.

Keywords

References

  1. Avontuur, J. A.,Boomsma, F.,van den Meiracker, A.,de Jong, F. H., and Bruining, H. A., Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock. Circulation., 99, 271-275 (1999) https://doi.org/10.1161/01.CIR.99.2.271
  2. Chen, Y. C., Shen, S. C., Chen, L. G., Lee, T. J., and Yang, L. L., Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expression induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem. Pharmacol., 61, 1417-1427 (2001) https://doi.org/10.1016/S0006-2952(01)00594-9
  3. Chi, Y. S., Lim, H., Park, H., and Kim, H. P., Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochem. Pharmacol., 66, 1271-1278 (2003) https://doi.org/10.1016/S0006-2952(03)00463-5
  4. Clausen, T. K., Scheibye, S., and Lawesson, S. O., N-Methylthiopyrrolidone. In Organic Synthesis, Freeman, J. P., Ed.; John Wiley: New York, CV. 7, 372-375 (1990)
  5. Dao, T. T., Kim, S. B., Sin, K.-S., Kim, S., Kim, H. P., and Park, H., Synthesis and biological activities of 8-arylflavones. Arch. Pharm. Res., 27, 278-282 (2004) https://doi.org/10.1007/BF02980059
  6. Dao, T. T., Chi, Y. S., Kim, J., Kim, H. P., Kim, S., and Park, H., Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives. Bioorg. Med. Chem. Lett., 14, 1165-1167 (2004) https://doi.org/10.1016/j.bmcl.2003.12.087
  7. Harborne, J. B., and Williams, C. A., Advances in flavonoids research since 1992. Phytochemistry, 55, 481-504 (2000) https://doi.org/10.1016/S0031-9422(00)00235-1
  8. Joo, Y. H., Lee, C. H., Noh, M. S., Ha, J. Y., Choi, J. K., Lim, K. M., Kim, J. K., and Kang, S. H., Diarylbenzopyran De rivatives as Cyclooxygenase-2 Inhibitors, US patent 6,340,694 (2002)
  9. Kim, H., Lee, H. S., Chang, K. T., Ko, T. H., Baek, K. J., and Kwon, N. S., Chloromethyl ketones block induction of nitric oxide synthase in murine macrophages by preventing activation of nuclear factor- Kappa B. J. Immunol., 154, 4741-4748 (1995)
  10. Kim, S. J., Park, H., and Kim, H. P., Inhibition of Nitric Oxide Production from Lipopolysaccharide-Treated RAW 264.7 Cells by Synthetic Flavones: Structure-Activity Relationship and Action Mechanism. Arch. Pharm. Res., 27, 937-943 (2004) https://doi.org/10.1007/BF02975847
  11. Lee, H., Kim, Y. O., Kim, H., Kim, S. Y., Noh, H. S., Kang, S. S., Cho, G. J., Choi, W. S., and Suk, K., Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J., 17, 1943-1944 (2003) https://doi.org/10.1096/fj.03-0057fje
  12. Lim, H., Park, H., and Kim, H. P., Inhibition of contact dermatitis in animal models and suppression of proinflammatory gene expression by topically applied flavonoid, wogonin. Arch. Pharm. Res., 27, 442-448 (2004) https://doi.org/10.1007/BF02980087
  13. Park, B. K., Heo, M. Y., Park, H., and Kim, H. P., Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix. Eur. J. Pharmacol., 425, 153-157 (2001) https://doi.org/10.1016/S0014-2999(01)01187-6
  14. Read, M. A., Flavonoids: naturally occurring anti-inflammatory agents. Am. J. Pathol., 147, 235-237 (1995)