Synthesis and cytotoxicity of kaempferol derivatives

doi:10.5246/jcps.2017.09.074

Abstract

Abstract:

In the present study, we developed a simple approach for the structural modifications of kaempferol (1). A new compound, 3,5-dihydroxy-2-(4-hydroxyphenyl)-6,8,8-tris(3-methylbut-2-en-1-yl)-4H-chromene-4,7(8H)-dione (5) together with three known compounds, 8-prenylkaempferol (2), 6-prenylkaempferol (3) and 6,8-diprenylkaempferol (4), were synthesized under different reaction conditions. All of derivatives were synthesized in a structural modification way for the first time. Their structures were primarily elucidated by NMR and MS analyses. Compounds 2, 3 and 5 exhibited prominent cytotoxic activity against MDA-231 (IC₅₀values were 9.45±0.20μM, 7.15±0.37 μM and 6.92±0.30 μM, respectively) and MCF-7 (IC₅₀values were 10.08±0.57μM, 10.04±0.23 μM and 2.15±0.20 μM,respectively) breast cancer cells.

Key words: Kaempferol, Derivatives, Structural modifications, Cytotoxicity

CLC Number:

R284

Supporting:

Yajing Ma, Huan Liu, Shunan Tang, Siwang Yu, Mingying Shang, Shaoqing Cai. Synthesis and cytotoxicity of kaempferol derivatives[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(9): 660-665.

References

[1] Miyamoto, M.; Matsushita, Y.; Kiyokawa, A.; Fukuda, C.; Iijima, Y.; Sugano, M.; Akiyama, T. Planta. Med., 1998, 64, 516–519.

[2] Power, K.A.; Zierau, O.; O'Dwyer, S. Hormone-Disruptive Chemical Contaminants in Food. Cambridge, RSC Publishing, 2012, 70–92.

[3] Shen, C.C.; Lin, T.W.; Huang, Y.L.; Wan, S.T.; Shien, B.J.; Chen, C.C. J. Nat. Prod. 2006, 69, 1237–1240.

[4] Basabe, P.; de Román, M.; Marcos, I.S.; Diez, D.; Blanco, A.; Bodero, O.; Mollinedo, F.; Sierra, B.G.; Urones, J.G. Eur. J. Med. Chem. 2010, 45, 4258–4269.

[5] Shang, M.Y.; Kong, Y.; Xiao, J.J.; Ma, X.J.; Ge, Y.W.; Cai, S.Q. China, Patent CN 101647842 B 2009, 20110831.

[6] Kong, Y.; Xiao, J.J.; Meng, S.C.; Dong, X.M.; Ge, Y.W.; Wang, R.F.; Shang, M.Y.; Cai, S.Q. Fitoterapia. 2010, 81, 367–370.

[7] Shang, M.Y.; Kong, Y.; Xiao, J.J.; Ma, X.J.; Ge, Y.W.; Cai, S.Q. China, Patent CN 101648934 A, 2009, 20100217.

[8] Kim, H.J.; Seo, J.Y.; Suh, H.J.; Lim, S.S.; Kim, J.S. Nutr. Res. Pract. 2012, 6, 491–498.

[9] Kumazawa, S.; Murase, M.; Momose, N.; Fukumoto, S. Asian. Pac. J. Trop. Med. 2014, 7, 16–20.

[10] Lin, K.W.; Liu, C.H.; Tu, H.Y.; Hornghuey, K.; Wei, B.L. Food. Chem. 2009, 115, 558–562.

[11] Li, H.F.; Guan, X.Y.; Yang, W.Z.; Liu, K.D.; Ye, M.; Sun, C.; Lu, S.; Guo, D.A. Fitoterapia. 2012, 83, 44–48.

[12] Yamada, Y.; Suzuki, K.; Mishima, S.; Suzuki, T. Patent 2009046414 A. 2009, 20090305.

[13] Lai, X.Q.; Ye, Y.X.; Sun, C.; Huang, X.; Tang, X.; Zeng, X.; Yin, P.; Zeng, Y. Int. Immunopharmacol. 2013, 16, 41–49.

[14] Peluso, M.R.; Miranda, C.L.; Hobbs, D.J.; Proteau, R.R.; Stevens, J.F. Planta. Med. 2010, 76, 1536–1543.

[15] Kim, J.H.; Lee, G.; Cho, Y.L.; Kim, C.K.; Han, S.; Lee, H.; Choi, J.S.; Choe, J.; Won, M.H.; Kwon, Y.G.; Ha, K.S.; Kim, Y.M. Eur. J. Pharmacol. 2009, 602, 422–431.

[16] Chen, C.C.; Tsai, P.C.; Chiou, W. Eur. J. Pharmacol. 2008, 590, 430–436.

[17] Jung, H.A.; Yoon, N.Y.; Kang, S.S.; Kim, Y.S.; Choi, J.S. J. Pharm. Pharmacol. 2008, 60, 1227–1236.

[18] Fukai, T.; Satoh, K.; Nomura, T.; Sakagami, H. Fitoterapia. 2003, 74, 720–724.

[19] Dong, X.; Qi, L.; Jiang, C.; Chen, J.; Wei, E.; Hu, Y. Bioorg. Med. Chem. Lett. 2009, 19, 3196–3198.

[20] Wo, Y.B.; Zhu, D.Y.; Hu, Y.; Wang, Z.Q.; Liu, J.; Lou, Y.J. J. Cell. Biochem. 2008, 103, 1536–1550.

[21] Wang, Q.H.; Guo, S.; Yang, X.Y.; Zhang Y.F.; Shang, M.Y.; Shang, Y.H.; Xiao, J.J.; Cai, S.Q. Chin. J. Nat. Med. 2017, 15, 225–233.

[22] Guo, S.; Wang, L.; Su, D.; Kong, Y.; Shang, M.Y.; Cai, S.Q. China Pharmacy. 2014, 25, 577–579.

[23] Zhang, L.H.; Bailong, Y.M.; Li, H. J. Med. Sci. Yanbian University. 2010, 33, 268–270.

[24] Li, X.; Yan, H.; Pang, X,; Sha, N.; Hua, H.; Wu, L.; Guo, D. Chin. J. Chin. Mat. 2009, 34, 282–285.

[25] Tanaka, T.; Iinuma, M.; Asai, F.; Ohyama, M.; Burandt, C.L. Phytochemistry. 1997, 46, 1431–1437.

[26] Yang, Y.; Zhang, H.; He, H.H.; Zhu, Z.H. Chin. Herb. Med. 2009, 40, 1026–1030.

[27] Sun, P.; Wen, Y.; Xu, Y.; Pei, Y.; Chen, Y.; Shimizu, N.; Takeda, T. Acta. Pharm. Sin. 1998, 33, 919–922.

[28] Kwon, H.J.; Kim, H.H.; Ryu, Y.B.; Kim, J.H.; Jeong, H.J.; Lee, S.W.; Chang, J. S.; Cho, K.O.; Rho, M.C.; Park, S.J. Bioorg. Med. Chem. 2010, 18, 7668–7674.

[29] Huang, K.F.; Chiang, J.Y. Chin. Pharm. J. 2004, 56, 133–139.

[30] Meragelman, K.M.; McKee, T.C.; Boyd, M.R. J. Nat. Prod. 2001, 64, 546–548.

[31] Yin, Q.; Xu, Z.; Zhang, Y.Q.; Zhang, W.H. Chin. J. Syn. Chem. 2011, 19, 578–581.

[32] Wang, H.M.; Yan, Z.H.; Lei, Y.N.; Kai, S.; Yao, Q.W.; Lu, K.; Yu, P. Tetrahedron. Lett. 2014, 55, 897–899.

[33] Shang, M.Y.; Li, J.; Cai, S.Q.; Li, P.; Xu, L.S.; Xu, G.J. Chin. Tradit. Herb. Drugs. 2000, 30, 569–571.

[34] Wang, Q.; Miao, W.J.; Xiang, C.; Guo, D.A.; Ye, M. Chin. Tradit. Herb. Drugs. 2014, 45, 31–36.
[35] Meragelman, K.M.; McKee, T.C.; Boyd, M.R. J. Nat. Prod. 2001, 64, 546–548.