Abstract
Eight ent-kaurene diterpenoids were isolated from three Isodon plants, Isodon excisoides (Sun ex C. H. Hu) C. Y. Wu et H. W. Li, Isodon weisiensis C. Y. Wu, and Isodon racemosa (Hemsl.) Hara. Their cytotoxicities were tested by SRB assay against four human tumor cell lines, HepG2, Tb, HO-8910 and SGC-7901. The DNA damage degrees on their Hep G2 cells were evaluated by Comet assay. The results showed that ent-kaurene diterpenoids were selectively toxic against these four tumor cell lines. Weisiensic C had the lowest cytotoxicity against four cell lines and degree of DNA damage on the Hep G2 cell line. Leukamenin E and Glaucocalyxin A had similar IC50 values and also induced a similar degree of DNA damage. The cytotoxicity and degree of DNA damage of eight ent-kaurene diterpenoids on Hep G2 was in the order Leukamenin E > Glaucocalyxin A > Wangzaozin A > Kamebanin > Macrocalyxin D > Weisiensin B > Excisanin K > Weisiensic C. The structure–activity relationships indicated that there was some correlation between the substituents and their structures of ent-kaurene diterpenoids and their activities on Hep G2 cells.
Similar content being viewed by others
References
Y. Min, Q. Gui-Qin, G. Hong-Zhu, G. De-An, J. Steroid Biochem. Mol. Biol. 91, 87 (2004)
M.T.D. Cronin, Farmaco 56, 149 (2001)
F. Lavelle, Pharmacol. Res. 31, 23 (1995)
M. Nakadate, Toxicol. Lett. 102–103, 627 (1998)
J.S. Jaworska, M. Comber, C. Auer, C.J. Van Leeuwen, Environ. Health Perspect. 111, 1358 (2003)
C. Lu-Ye, Ch. Zi-Jun, Yunnan J. Tradit. Chin. Med. Mater. Med. 25, 42 (2004)
Y. Dong-juan, M. Rui-jun, W. Lai, L. Guo-an, W. Han, D. Lan, J. Sichuan Univ. (Nat. Sci. Ed.) 42, 1038 (2005)
H.D. Sun, Y.L. Xu, B. Jiang, Diterpenoids from Isodon species (Science Press, Beijing, 2001)
E. Fujita, Y. Nagao, M. Node, K. Kaneko, S. Nakazawa, H. Kuroda, Experientia 32, 203 (1976)
J. Liu, J.Y. Liang, T. Xie, Strait Pharm. J. 16, 1 (2004)
A. Urzúa, F. Jara, E. Tojo, M. Wilkens, L. Mendoza, M.C. Rezende, J. Ethnopharmacol. 103, 297 (2006)
M. Wilkens, C. Alarcon, A. Urzua, L. Mendoza, Plant. Med. 68, 452 (2002)
I. Suzuki, M. Kondoh, F. Nagashima, M. Fujii, Y. Asakawa, Y. Watanabe, Plant. Med. 70, 401 (2004)
G.A. Liu, L. Ding, Y. Yang, H. Yang, Q.M. Yang, H.Q. Wang, Res. Chem. Intermed. 32, 787 (2006)
Q.B. Han, J.X. Zhang, Y. Lu, Y.S. Wu, Q.T. Zheng, H.D. Sun, Plant. Med. 70, 581 (2004)
B. Jiang, Z.Q. Lu, A.J. Hou, Q.S. Zhao, H.D. Sun, J. Nat. Prod. 62, 941 (1999)
I.S. Lee, L.A. Shamon, H.B. Chai, T.E. Chagwedera, J.M. Besterman, N.R. Farnsworth, Chem-Biol. Interact. 99, 193 (1996)
X. Li, W.L. Xiao, J.X. Pu, L.L. Ban, Y.H. Shen, Z.Y. Weng, Phytochemistry 67, 1336 (2006)
Y. Higuchi, Biochem. Pharmacol. 66, 1527 (2003)
W.P. Roos, B. Kaina, Trends Mol. Med. 12, 440 (2006)
A. Barzilai, Antioxid. Redox Signal. 9, 211 (2007)
O. Ostling, K.J. Johanson, Biochem. Biophys. Res. Commun. 123, 291 (1984)
R.R. Tice, E. Agurell, D. Anderson, B. Burlinson, A. Hartmann, H. Kobayashi, Environ. Mol. Mutagen. 35, 206 (2000)
A. Nowak, P. Chow, M. Findlay, Eur. J. Cancer 40, 1474 (2004)
S. Knasmüller, W. Parzefall, R. Sanyal, S. Ecker, C. Schwab, M. Uhl, V.M. Sun-dermann, G. Williamson, G. Hietsch, T. Langer, F. Darroudi, A.T. Natarajan, Mutat. Res./Fundam. Mol. Mech. Mutagen. 402, 185 (1998)
K.T. Papazisis, G.D. Geromichalos, K.A. Dimitriadis, A.H. Kortsaris, J. Immunol. Methods 208, 151 (1997)
N.P. Singh, M.T. McCoy, R.R. Tice, E.L. Schneider, Exp. Cell Res. 175, 184 (1988)
S.M. Everett, K.L. White, C.J. Schorah, R.J. Calvert, C. Skinner, D. Miller, Mutat. Res. Genet. Toxicol. Environ. Mutagen. 468, 73 (2000)
Y. Aoyagi, M.Y. Gui, Y.R. Jin, X.W. Li, T. Noguchi, H. Fukaya, T. Hasuda, K. Takeya, Tetrahedron Lett. 45, 1421 (2004)
K.R. Wang, B.Z. Zhang, W. Zhang, J.X. Yan, J. Li, R. Wang, Peptides 29, 963 (2008)
J. Liu, W.X. Hu, L.F. He, M. Ye, Y. Li, FEBS Lett. 578, 245 (2004)
H.M. Kim, S.B. Han, M.S. Kim, J. Pharmacol. Toxicol. Methods 36, 163 (1996)
A. Itharat, P.J. Houghton, E. Eno-Amooquaye, P.J. Burke, J.H. Sampson, A. Raman, J. Ethnopharmacol. 90, 33 (2004)
P. Daza, J. Torreblanca, F.J. Moreno, Cell Biol. Int. 28, 497 (2004)
T. Fujita, Y. Takeda, E. Yuasa, A. Okamura, T. Shingu, T. Yokoi, Phytochemistry 21, 903 (1982)
L.M. Li, G.Y. Li, L.S. Ding, C. Lei, L.B. Yang, Y. Zhao, Tetrahedron Lett. 48, 9100 (2007)
S.X. Huang, Y. Zhou, J.X. Pu, R.T. Li, X. Li, W.L. Xiao, Tetrahedron 62, 4941 (2006)
Acknowledgments
This research was supported by the Key (Key grant) Project of Chinese Ministry of Education (208147), the Research Foundation of Education Department of Gansu Province (0601-27), the National Natural Science Foundation of China (No-30960464) and the Foundation of the Innovation Project Council of Northwest Normal University (NWNU-KJCXGC-03–65).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ding, L., Hou, Q., Zhou, Q. et al. Structure–activity relationships of eight ent-kaurene diterpenoids from three Isodon plants. Res Chem Intermed 36, 443–452 (2010). https://doi.org/10.1007/s11164-010-0144-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11164-010-0144-3