SIOC 中文
CJOG
Adv search

Chinese Journal of Organic Chemistry >

2014 , Vol. 34 >Issue 8: 1603 - 1608

DOI: https://doi.org/10.6023/cjoc201403046

Articles

Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412

  • Wang Liping ,
  • Zhuang Yibin ,
  • Sun Kunlai ,
  • Zhu Weiming
Expand
  • Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003

Received date: 2014-03-20

  Revised date: 2014-04-12

  Online published: 2014-05-05

Supported by

Project supported by the National Basic Research Program of China (No. 2010CB833804), the National Natural Science Foundation of China (Nos. 41376148, 21172204, 30572246), and the National High-Tech R&D Program of China (Nos. 2013AA092901, 2012AA092104, 2007AA091502).

Fold

Abstract

Twelve new halogenated derivatives of PKC-412 were synthesized from the marine microbial natural product, staurosporine. Their structures were identified by 1H NMR, 13C NMR, IR and HRESIMS. The cytotoxicities of these halogenated derivatives against HL-60, A549 and hela cell lines were evaluated using thiazolyl blue tetrazolium bromide (MTT) method. The results showed that compounds 4 and 10 displayed comparative cytotoxicity of PKC-412 against HL-60 and A549 cell lines with IC50 values of 0.5～0.95 μmol·L-1, and the halogenation on phenyl nucleus of benzamide moiety increased the selectivity of compounds to A549 cell, indicating a worth of further study.

Key words： staurosporine; PKC-412; halo-derivatives; cytotoxicity

Cite this article

Wang Liping , Zhuang Yibin , Sun Kunlai , Zhu Weiming . Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412[J]. Chinese Journal of Organic Chemistry, 2014 , 34(8) : 1603 -1608 . DOI: 10.6023/cjoc201403046

References

[1] Zhao, C.; Zhu, T.; Zhu, W. Chin. J. Org. Chem. 2013, 33, 1195 (in Chinese).
(赵成英, 朱统汉, 朱伟明, 有机化学, 2013, 33, 1195.)
[2] Omura, S.; Iwai, Y.; Hirano, A.; Nakagawa, A.; Awaya, J.; Tsuchiya, H.; Takahashi, Y.; Masuma, R. J. Antibiot. 1977, 30, 275.
[3] Bharate, S. B.; Sawant, S. D.; Singh, P. P.; Vishwakarma, R. A. Chem. Rev. 2013, 113, 6761.
[4] El, F. J.; Su, Y.; Büchler, P.; Ludwig, R.; Giese, N. A.; Büchler, M. W.; Quentmeier, H.; Hines, O. J.; Herr, I.; Friess, H. Cancer 2007, 110, 1457.
[5] Wachtel, M.; Schafer, B. W.; Amstutz, R. WO 2007054579, 2007[Chem. Abstr. 2007, 146, 507692].
(Fabbro, D.; Wachtel, M.; Schafer, B. W.; Amstutz, R.; Troxler, H.; Kleinert, P.; Niggli, F. K. WO 2007054579, 2007[Chem. Abstr. 2007, 146, 507692].
[6] George, P.; Bali, P.; Cohen, P.; Tao, J.; Guo, F.; Sigua, C.; Vishvanath, A.; Fiskus, W.; Scuto, A.; Annavarapu, S.; Moscinski, L.; Bhalla, K. Cancer Res. 2004, 64, 3645.
[7] Weisberg, E.; Boulton, C.; Kelly, L. M.; Manley, P.; Fabbro, D.; Meyer, T.; Gilliland, D. G.; Griffin, J. D. Cancer Cell 2002, 1, 433.
[8] Wang, Y. F.; Yin, O. Q. P.; Graf, P.; Kisicki, J. C.; Schran, H. J. Clin. Pharmacol. 2008, 48, 763.
[9] del Corral, A.; Dutreix C.; Huntsman-Labed A.; Lorenzo S.; Morganroth J.; Harrell R.; Wang Y. Cancer Chemother. Pharmacol. 2012, 69,1255.
[10] Fischer T.; Stone, R. M.; Deangelo, D. J.; Galinsky, I.; Estey, E.; Lanza, C.; Fox, E.; Ehninger, G.; Feldman, E. J.; Schiller, G. J.; Klimek, V. M.; Nimer, S. D.; Gilliland, D. G.; Dutreix, C.; Huntsman-Labed, A.; Virkus, J.; Giles, F. J. J. Clin. Oncol. 2010, 28, 4339.
[11] Lu, Y.; Shi, T.; Wang, Y.; Yang, H.; Yan, X.; Luo, X.; Jiang, H.; Zhu, W. J. Med. Chem. 2009, 52, 2854.
[12] Zhu, W. M.; Zhuang, Y. B.; Wang, Y.; Liu, P. P. CN 102101866, 2011 [Chem. Abstr. 2011, 155, 123598].
[13] Yang, S. M.; Malaviya, R.; Wilson, L. J.; Argentieri, R.; Chen, X.; Yang, C.; Wang, B.; Cavender, D.; Murray, W. V. Bioorg. Med. Chem. Lett. 2007, 17, 326.
Options
Outlines

/

〈 〉