Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412

doi:10.6023/cjoc201403046

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (8): 1603-1608.DOI: 10.6023/cjoc201403046 Previous Articles Next Articles

Articles

PKC-412卤代衍生物的合成及细胞毒活性研究

王立平, 庄以彬, 孙坤来, 朱伟明

中国海洋大学医药学院海洋药物教育部重点实验室青岛 266003

收稿日期:2014-03-20 修回日期:2014-04-12 发布日期:2014-05-05
通讯作者: 朱伟明 E-mail:weimingzhu@ouc.edu.cn
基金资助:
国家重点基础研究发展计划（No.2010CB833804）、国家自然科学基金（Nos.41376148，21172204，30572246）和高科技发展计划（Nos.2013AA092901，2012AA092104，2007AA091502）资助项目.

Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412

Wang Liping, Zhuang Yibin, Sun Kunlai, Zhu Weiming

Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003

Received:2014-03-20 Revised:2014-04-12 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).

1. Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412.PDF(2216KB)

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

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Wang Liping, Zhuang Yibin, Sun Kunlai, Zhu Weiming. Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412[J]. Chin. J. Org. Chem., 2014, 34(8): 1603-1608.

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[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.

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PKC-412卤代衍生物的合成及细胞毒活性研究

Synthesis and Cytotoxicity of Halogenated Derivatives of PKC-412

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