Synthesis and Antitumor Activities of β-Carboline Derivatives

doi:10.6023/cjoc201208035

Chin. J. Org. Chem. ›› 2013, Vol. 33 ›› Issue (02): 332-338.DOI: 10.6023/cjoc201208035 Previous Articles Next Articles

Articles

β-咔啉衍生物的合成和初步抗肿瘤活性研究

郭亮^a, 范文玺^a, 陈雪梅^a, 马芹^a, 曹日晖^a,b

a 新疆华世丹药物研究有限责任公司乌鲁木齐 830011;
b 中山大学化学与化学工程学院广州 510275

收稿日期:2012-08-30 修回日期:2012-11-01 发布日期:2012-11-14
通讯作者: 曹日晖 E-mail:caorihui@mail.sysu.edu.cn
基金资助:
国家“重大新药创制”科技重大专项(No. 2009ZX09401-007)资助项目.

Synthesis and Antitumor Activities of β-Carboline Derivatives

Guo Liang^a, Fan Wenxi^a, Chen Xuemei^a, Ma Qin^a, Cao Rihui^a,b

a Xinjiang Huashidan Pharmaceutical Research Co., Ltd., Urumqi 830011;
b School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275

Received:2012-08-30 Revised:2012-11-01 Published:2012-11-14
Supported by:
Project supported by the National Key Program for New Drug Development (No. 2009ZX09401-007).

In search of more effective antitumor agents, based on the previous results of computer aided drug design. The starting material L-tryptophan reacted with formaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the intermediate β-carboline. The intermediate was further reacted with halogenated hydrocarbon by N⁹-alkylation and N²-quaternarization to obtain new β-carboline derivatives. Fourteennovel β-carboline derivatives were synthesized and characterized by ¹H NMR, IR, MS and elemental analysis. Compound 5h was further studied by X-ray single crystal diffraction analysis. The antitumor activity of the target compounds was studied by MTT method. The results demonstrated that N²-quaternarized compounds (5a～5n) had more remarkable cytotoxic activities in vitro than 9-phenylpropyl-β-carboline (4). The tumor inhibition rates of the selected compounds 5e and 5h in mice bearing Lewis lung cancer. The compound 9 showed inhibition activity on transplanting-tumor growth of Lewis lung cancer.

Key words: β-carboline, synthesis, antitumor activity, structure-activity relationship

Cite this article

Guo Liang, Fan Wenxi, Chen Xuemei, Ma Qin, Cao Rihui. Synthesis and Antitumor Activities of β-Carboline Derivatives[J]. Chin. J. Org. Chem., 2013, 33(02): 332-338.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Jiao, W.-H.; Gao, H.; Li, C.-Y.; Zhao, F.; Jiang, R.-W.; Wang, Y.; Zhou, G.-X.; Yao, X.-S. J. Nat. Prod. 2010, 73, 167.

[2] Takahashi, Y.; Ishiyama, H.; Kubota, T.; Kobayashi, J. Bioorg. Med. Chem. Lett. 2010, 20, 4100.

[3] Michael, C.; Robert, W. W.; Fil, G.; James, M. C.; Steven, A. B.; Kenner, C. R.; Jacqueline, N. C.; Steven, M. P.; Phil, S. J. Med. Chem. 1982, 25, 1081.

[4] Lin, W.; Xiao, S.-L.; Yang, M. J. Peking Univ. (Health Sci.) 2001, 33, 277 ( in Chinese). (林伟, 肖苏龙, 杨铭, 北京大学学报(医学版), 2001, 33, 277.)

[5] Ishida, J.; Wang, H.-K.; Bastow, K. F.; Hu, C.-Q.; Lee, K.-H. Bioorg. Med. Chem. Lett. 1999, 9, 3319.

[6] Rashid, M. A.; Gustafson, K. R.; Boyd, M. R. J. Nat. Prod. 2001, 64, 1454.

[7] Kuo, P.-C.; Shi, L.-S.; Damu, A. G.; Su, C.-R.; Huang, C.-H.; Ke, C.-H.; Wu, J.-B.; Lin, A.-J.; Bastow, K. F.; Lee, K.-H.; Wu, T.-S. J. Nat. Prod. 2003, 66, 1324.

[8] Rivas, P.; Cassels, B. K.; Morello, A. Comp. Biochem. Physiol., Part C 1999, 122, 27.

[9] Srivastava, S. K.; Agarwal, A.; Chauhan, P. M. S.; Agarwal, S. K.; Bhaduri, A. P.; Singh, S. N.; Fatima, N.; Chatterjee, R. K. Bioorg. Med. Chem. 1999, 7, 1223.

[10] Xu, G.-Y.; Zhou, Y.; Zuo, G.-L.; Jiang, Y.-J. Chin. J. Org. Chem. 2009, 29, 1593 (in Chinese). (徐广宇, 周伊, 左高磊, 蒋勇军, 有机化学, 2009, 29, 1593.)

[11] Cao, R.-H. Ph.D. Dissertation, Sun Yat-sen University, Guangzhou, 2004 (in Chinese). (曹日晖, 博士论文, 中山大学, 广州, 2004.)

[12] Cao, R.-H.; Peng, W.-L.; Wang, Z.-H.; Xu, A.-L. Curr. Med. Chem. 2007, 14, 479.

[13] Cao, R.-H.; Peng, W.-L.; Chen, H.-X.; Hou, X.-R.; Guan, H.-J.; Ma, Y.; Xu, A.-L. Eur. J. Med. Chem. 2005, 40, 249.

[14] Cao, R.-H.; Chen, H.-X.; Peng, W.-L.; Ma, Y.; Hou, X.-R.; Guan, H.-J.; Liu, X.-D.; Xu, A.-L. Eur. J. Med. Chem. 2005, 40, 991.

[15] Cao, R.-H.; Yi W.; Wu, Q.-F.; Guan, X.-D.; Feng, M.-X.; Ma, C.-M.; Chen, Z.-Y.; Song, H.-C; Peng, W.-L. Bioorg. Med. Chem. Lett. 2008, 18, 6558.

[16] Cao, R.-H.; Guan, X.-D.; Shi, B.-X.; Chen, Z.-Y.; Ren, Z.-H.; Peng, W.-L.; Song, H.-C. Eur. J. Med. Chem. 2010, 45, 2503.

[17] Ma, C.-M.; Cao, R.-H.; Shi, B.-X.; Zhou, X.-T.; Ma, Q.; Sun, J.; Guo, L.; Yi W.; Chen, Z.-Y.; Song, H.-C. Eur. J. Med. Chem. 2010, 45, 5513.

[18] Chen, Z.-Y.; Cao, R.-H.; Shi, B.-X.; Guo, L.; Sun, J.; Ma, Q.; Fan, W.-X.; Song, H.-C. Eur. J. Med. Chem. 2011, 46, 5127.

[19] Guo, L.; Sun, J.; Fan, W.-X.; Ma, Q. Chin. J. Modern Appl. Pharm. 2012, 29, 385 (in Chinese). (郭亮, 孙洁, 范文玺, 马芹, 中国现代应用药学, 2012, 29, 385.)

[20] Zhou, S.-S.; Xue, X.; Jiang, B.; Lu, C.-H.; Tian, Y.-P.; Jiang, M.-H. Acta Chim. Sinica 2011, 69, 2335 (in Chinese). (周双生, 薛璇, 姜波, 鲁传华, 田玉鹏, 蒋明华, 化学学报, 2011, 69, 2335.)

[21] Zou, X.-J.; Liu, Y.; Liu, Z.-M.; Gao, J.-W.; Song, Q.-L.; Pan, Y.; Zhang, J.-Z.; Li, X.-J.; Lai, L.-H. Chin. J. Org. Chem. 2011, 31, 1923 (in Chinese). (邹霞娟, 刘莹, 刘振明, 高军卫, 宋前流, 潘燕, 张剑钊, 李学军, 来鲁华, 有机化学, 2011, 31, 1923.)

β-咔啉衍生物的合成和初步抗肿瘤活性研究

Synthesis and Antitumor Activities of β-Carboline Derivatives

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Penghui Li, Qingyang Xie, Fuxian Wan, Yuanhong Zhang, Lin Jiang. Synthesis and Fungicidal Activity of Novel Substituted Pyrimidine-5-carboxamides Bearing Cyclopropyl Moiety [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 650-656.
[2]	Fakai Zou, Nengzhong Wang, Hui Yao, Hui Wang, Mingguo Liu, Nianyu Huang. Regio- and Stereo-selective Synthesis of 1β-/3R-Aryl Thiosugar [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 593-604.
[3]	Luyao Li, Zhongwen He, Zhenguo Zhang, Zhenhua Jia, Teck-Peng Loh. Application of Triaryl Carbenium in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 421-437.
[4]	Qinggang Mei, Qinghan Li. Recent Progress of Visible Light-Induced the Synthesis of C(3) (Hetero)arylthio Indole Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(2): 398-408.
[5]	Haibo Huo, Guixia Li, Shijun Wang, Chun Han, Baojun Shi, Jian Li. Novel γ-Carboline Derivatives as Antibacterial Agents: Synthesis and Antibacterial Evaluation [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 204-215.
[6]	Weiqing Yang, Yanbing Ge, Yuanyuan Chen, Ping Liu, Haiyan Fu, Menglin Ma. Design and Synthesis of Fluorescent 1,8-Napthalimide Derivatives and Their Identification of Cysteine [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 180-194.
[7]	Shihang Yu, Jiawei Liu, Biyu An, Qinghua Bian, Min Wang, Jiangchun Zhong. Asymmetric Synthesis of the Contact Sex Pheromone of Neoclytus acuminatus acuminatus (Fabricius) [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 301-308.
[8]	Qianfan Zhao, Yongzheng Chen, Shiming Zhang. Application and Mechanism Study of Carbon-Based Metal-Free Catalysts in Organic Synthesis [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 137-147.
[9]	Shan Chen, Zhilin Chen, Qiong Hu, Yanshuang Meng, Yue Huang, Pingfang Tao, Liru Lu, Guobao Huang. Recognition of Bis-thiourea Tweezers to Neutral Molecules in Non-Polar Solvent [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 277-281.
[10]	Huakun Wang, Xiaolong Ren, Yining Xuan. Study of the Halide Salt Catalyzed [3＋2] Cycloaddition of α,β-Epoxy Carboxylate with Isocyanate [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 251-258.
[11]	Yukun Jin, Baoyi Ren, Fushun Liang. Visible Light-Mediated Selective C—F Bond Cleavage of Trifluoromethyl Groups and Its Application in Synthesizing gem-Difluoro-Containing Compounds [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 85-110.
[12]	Cuiyun Ma, Hailan Luo, Fuhua Zhang, Dan Guo, Shuxing Chen, Fei Wang. Green Biosynthesis, Photophysical Properties and Application of 3-Pyrrolyl BODIPY [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 216-223.
[13]	Bozhen Wang, Jie Zhang, Chunhui Nian, Mingming Jin, Miaomiao Kong, Wulan Li, Wenfei He, Jianzhang Wu. Synthesis and Antitumor Activity of 3,4-Dichlorophenyl Amides [J]. Chinese Journal of Organic Chemistry, 2024, 44(1): 232-241.
[14]	Ruixia Cao, Yuping Jia. Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3304-3311.
[15]	Huanqing Li, Zhaohua Chen, Zujia Chen, Qiwen Qiu, Youcai Zhang, Sihong Chen, Zhaoyang Wang. Research Progress in Mercury Ion Fluorescence Probes Based on Organic Small Molecules [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3067-3077.