Archives of Pharmacal Research

, Volume 31, Issue 11, pp 1413–1418 | Cite as

Topoisomerase I and II inhibitory constituents from the bark of Tilia amurensis

  • Jae-Young Choi
  • Chang-Seob Seo
  • Ming-Shan Zheng
  • Chong-Soon Lee
  • Jong-Keun SonEmail author
Research Article Drug Efficacy and Safety


Two coumarins (1 and 6), one flavan-3-ol (2), one fatty acid (3), and two lignan glycosides (4 and 5) were isolated from the EtOAc and CH2Cl2 extract of the bark of Tilia amurensis. Their chemical structures were identified by comparing their physicochemical and spectral data with those of published in literatures. Compounds 4, 5, and 6 were isolated from Tilia genus for the first time. Compounds 2 and 3 showed potent inhibitory activity against both DNA topoisomerase I (IC50 values; 49 μM and 4 μM, respectively, with 18 μM of positive control compound, comptothecin) and DNA topoisomerase II (IC50 values; 13 μM and 3 μM, respectively, with 50 μM of positive control compound, etoposide). However, all compounds did not showed cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7), and human liver hepatoblastoma cell line (HepG-2).

Key words

Tilia amurensis Tiliaceae DNA topoisomerase I DNA topoisomerase II Cytotoxicity 


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  1. Ahn, D. K., Illustrated Book of Korean Medicinal Herbs, Kyohak Publishing Co., Ltd., Seoul, pp. 56, (2003).Google Scholar
  2. Aydin, S., Öztürk, Y., Baser, K. H. C, Kirimer, N., and Kurtaröztürk, N., Effects of Alcea pallid L (A) and Tilia argentea Desf Ex Dc infusions on swimming performance in mice. Phytother. Res., 6, 219–220 (1992).CrossRefGoogle Scholar
  3. Bailly, C., Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs. Crit. Rev. Oncol. Hematol., 45, 91–108 (2003).PubMedCrossRefGoogle Scholar
  4. Chen, A. Y. and Liu, L. F., DNA topoisomerases: essential enzymes and lethal targets. Annu. Rev. Pharmacol. Toxicol., 34, 191–218 (1994).PubMedCrossRefGoogle Scholar
  5. Foo, L. Y. and Karchesy, J. J., Procyanidin dimers and trimers from Douglas fir inner bark. Phytochemistry, 28, 1743–1747 (1989).CrossRefGoogle Scholar
  6. Foo, L. Y., Newman, R., Waghorn, G., Mcnabb, W. C., and Ulyatt, M. J., Proanthocyanidins from Lotus corniculatus. Phytochemistry, 41, 617–624 (1996).CrossRefGoogle Scholar
  7. Fukuda, M., Nishio, K., Kanzawa, F., Ogasawara, H., Ishida, T., Arioka, H., Bojamowski, k., Oka, M. and Saijo, N., Synergism between cisplatin and topoisomerase I inhibitors, NB-506 and SN-38, in human small cell lung cancer cells. Cancer Res., 56, 789–793 (1996).PubMedGoogle Scholar
  8. Hickok, L. G. and Anway, J. C., A morphological and chemical analysis of geographical variation in Tilia L. of eastern North America. Brittonia, 24, 2–8 (1972).CrossRefGoogle Scholar
  9. Kato, T., Yamaguchi, Y., Hirukawa, T., and Hoshino, N., Structural elucidation of naturally occurring 9,12,13-trihydroxy fatty acids by a synthetic study. Agric. Biol, Chem., 55(5), 1349–1357 (1991).Google Scholar
  10. Kim, C. M., Kang, S. S., Park, Y. S., and Kim, E. Y., Studies on the chemical constituents of Tilia plants in Korea (I). On the chemical constituents of the stem-bark of Tilia mandsurica. Kor. J. Pharmacogn., 19, 174–176 (1988).Google Scholar
  11. Lee, J. H., Lee, K. T., Yang, J. H., Baek, N. I., and Kim, D. K., Acetylcholinesterase inhibitors from the twihg of Vaccinium oldhami Miquel. Arch. Pharm. Res., 27, 53–56 (2004).PubMedCrossRefGoogle Scholar
  12. Lee, M. K., Sung, S. H., Lee, H. S., Cho, J. H., and Kim, Y. C., Lignan and neolignan glycosides from Ulmus davidiana var. japonica. Arch. Pharm. Res., 24, 198–201 (2001).PubMedCrossRefGoogle Scholar
  13. Lee, S. H., Kim, K. S., Shim, S. H., Park, Y. M., and Kim B. K., Constituents from the non-polar fraction of Artemisia apiacea. Arch. Pharm. Res., 26, 902–905 (2003).PubMedCrossRefGoogle Scholar
  14. Matsuda, H., Ninomiya, K., Shimoda, H., and Yoshikawa, M., Hepatoprotective principles from the flowers of Tilia argentea (Linden): Structure requirements of tiliroside and mechanism of action. Bioorg. Med. Chem., 10, 707–712 (2002).PubMedCrossRefGoogle Scholar
  15. Nonaka, G., Kawahara, O., and Nishioka, I. Tannins and related comounds. XV. A new class of dimeric flavan-3-ol gallates, theasinensins A and B, and prodanthocyanidin gallates from Green tea leaf. (1). Chem. Pharm. Bull., 31, 3906–3914 (1983).Google Scholar
  16. Park, J. H., Medicinal Plants of Korea, Shinil Book Co., Seoul, pp. 896–900, (2004).Google Scholar
  17. Pietta, P., High-performance liquid chromatography and micellar electrokinetic chromatography of flavonol glycosides from Tilia. J. Chromatogr., 638, 357–361 (1993).CrossRefGoogle Scholar
  18. Pommier, Y., Diversity of DNA topoisomerases I and inhibitors. Biochimie, 80, 255–270 (1998).PubMedCrossRefGoogle Scholar
  19. Potmesil, M., Camptothecins: from bench research to hospital wards. Cancer Res., 54, 1431–1439 (1994).PubMedGoogle Scholar
  20. Pramod, T. J., Frank, A. F., Joyce, K. R., Michael, S. O., and David, G., Induction of DNA synthesis, and suppression of c-myc expression by the topoisomerase I inhibitor, Campththecin, in MCF-7 human breast tumor cells. Biochem. Pharm., 55, 1263–1269 (1998).CrossRefGoogle Scholar
  21. Rubinstein, L. V., Shoemaker, R. H., Paul, K. D., Simon, R. M., Tosini, S., Skehan, P., Scudiero, D. A., Monks, A., and Boyd, M. R., Comparison of in vitro anticancer-drugscreening data generated with a lines. J. Nat. Cancer Inst., 82, 1113–1118 (1990).PubMedCrossRefGoogle Scholar
  22. Slichenmyer, W. J., Rowinsky, E. K., Donehower, R. C., and Kaufmann, S. H., The current status of camptothecin analogues as antitumor agents. J. Natl. Cancer Inst., 85, 271–291 (1993).PubMedCrossRefGoogle Scholar
  23. Šmite, E., Pan, H., and Lundgren, L. N., Lignan glycosides from inner bark of Betula pendula. Phytochemistry, 40(1), 341–343 (1995).CrossRefGoogle Scholar
  24. Suemune, H., Harabe, T., and Sakai, K., Syntheses of unsaturated trihydroxy C-18 fatty acids isolated from rice plants suffering from rice blast disease. Chem. Pharm. Bull., 36(9), 3632–3627 (1988).Google Scholar
  25. Toker, G., Küpeli, E., Memisoðlu, M., and Yesilada, E., Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden). J. Ethnopharmacol., 95, 393–397 (2004).PubMedCrossRefGoogle Scholar
  26. Viola, H., Wolfman, C., Destein, M. L., Wasowski, C., Pena, C., Medina, J. H., and Paladine, A. C., Isolation of pharmacologically active benzodiazepine receptor ligands from Tilia tomentosa (Tiliceae). J. Ethnopharmacol., 44, 47–53 (1994).PubMedCrossRefGoogle Scholar
  27. Wang, J. C., Recent studies of DNA topoisomerases. Biochim, Biophys. Acta., 904, 1–9 (1987).CrossRefGoogle Scholar
  28. Yu, Y. P., Kang, S. S., and Kim, C. M., A study on the chemical constituents of Tilia koreana Nakai. Kor. J. Pharmacogn., 21, 265–269 (1990).Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2008

Authors and Affiliations

  • Jae-Young Choi
    • 1
  • Chang-Seob Seo
    • 1
  • Ming-Shan Zheng
    • 1
  • Chong-Soon Lee
    • 2
    • 1
  • Jong-Keun Son
    • 1
    Email author
  1. 1.College of PharmacyYeungnam UniversityGyongsanKorea
  2. 2.Department of Biochemistry, College of ScienceYeungnam UniversityGyongsanKorea

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