Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

doi:10.1007/s40242-013-3336-8

高等学校化学研究 ›› 2013, Vol. 29 ›› Issue (5): 906-910.doi: 10.1007/s40242-013-3336-8

Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

LUO Hao-ming^1,2, YANG Chun-ling², ZHANG Xiao-ying³, ZHAO Ming-ming⁴, JIANG Dan², XIAO Jun-hai², YANG Xiao-hong¹, LI Song²

1. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China;
2. National Engineering Research Center for the Strategic Drugs, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P. R. China;
3. The First Hospital of Jilin University, Changchun 130021, P. R. China;
4. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

收稿日期:2013-08-06 修回日期:2013-08-30 出版日期:2013-10-01 发布日期:2013-09-17
通讯作者: XIAO Jun-hai, YANG Xiao-hong E-mail:xiaojunhai@139.com;xiaohongyang88@126.com
基金资助:
Supported by the National Natural Science Foundation of China(Nos.20771030, 20671025).

Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

LUO Hao-ming^1,2, YANG Chun-ling², ZHANG Xiao-ying³, ZHAO Ming-ming⁴, JIANG Dan², XIAO Jun-hai², YANG Xiao-hong¹, LI Song²

1. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China;
2. National Engineering Research Center for the Strategic Drugs, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P. R. China;
3. The First Hospital of Jilin University, Changchun 130021, P. R. China;
4. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2013-08-06 Revised:2013-08-30 Online:2013-10-01 Published:2013-09-17
Contact: XIAO Jun-hai, YANG Xiao-hong E-mail:xiaojunhai@139.com;xiaohongyang88@126.com
Supported by:
Supported by the National Natural Science Foundation of China(Nos.20771030, 20671025).

摘要/Abstract

摘要：

A novel series of first procaspase activating compound(PAC-1) analogues was designed, synthesized and evaluated for antitumor activity towards two cell lines[human promyelocytic leukemia cell line(HL60) and human embryonic lung fibroblast cell line(HLF)] by the MTT[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazo-liumromide] method in vitro. The structures of all the compounds were confirmed by ¹H NMR, MS and elemental analysis. Among the compounds synthesized,(E)-2-[(3-{[4-(tert-butyl)benzyl](methyl)amino}propyl)(methyl)amino]-N'-[4-(diethylamino)-2-hydroxybenzylidene]acetohydrazide(compound 6n) exhibits a good anti-proliferative activity to the majority of tumor cells tested, and selectively cleaves cancer cells. Thus, compound 6n was identified as promising lead compound for further structural modification.

关键词: PAC-1 analogue, Anticancer activity, MTT assay, HL60

Abstract:

Key words: PAC-1 analogue, Anticancer activity, MTT assay, HL60

LUO Hao-ming, YANG Chun-ling, ZHANG Xiao-ying, ZHAO Ming-ming, JIANG Dan, XIAO Jun-hai, YANG Xiao-hong, LI Song. Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues[J]. 高等学校化学研究, 2013, 29(5): 906-910.

参考文献

[1] Igney F. H., Krammer P. H., Nature Rev. Cancer, 2002, 2, 277
[2] Zornig M., Hueber A. O., Baum W., Evan G., Biochim. Biophys. Acta, 2001, 1551, F1
[3] Su J. Q., Chi B. R., Li X., Liu L., Liu L. M., Qi Y. X., Wang Z. Y., Jin N. Y., Chem. Res. Chinese Universites, 2012, 28(3), 465
[4] Hu W., Kavanagh J. J., Lancet Oncol., 2003, 4, 721
[5] Hanahan D., Weinberg R., Cell, 2011, 144, 646
[6] Earnshaw W. C., Martins L. M., Kaufmann S. H. Annu. Rev. Biochem., 1999, 68, 383
[7] Hanahan D., Weinberg R., Cell, 2000, 100, 57
[8] Fesik S. W., Nat. Rev. Cancer, 2005, 5, 876
[9] Peterson Q. P., Goode D. R., West D. C. Ramsey K. N., Lee J. J. Y., Hergenrother P. J., J. Mol. Biol., 2009, 388, 144
[10] Boatright K. M., Salvesen G. S., Curr. Opin. Cell Biol., 2003, 15, 725
[11] Luthi A. U., Martin S. J., Cell Death Differ., 2007, 14, 641
[12] Timmer J. C., Salvesen G. S., Cell Death Differ., 2007, 14, 66
[13] Roy S., Bayly C. I., Gareau Y., Houtzager V. M., Kargman S., Keen S. L., Rowland K., Seiden I. M., Thornberry N. A., Nicholson D. W., Proc. Natl. Acad. Sci. USA, 2001, 98, 6132
[14] Putt K. S., Chen G. W., Pearson J. M., Sandhorst J. S., Hoagland M. S., Kwon J. T., Hwang S. K., Jin H., Churchwell M. I., Cho M. H., Doerge D. R., Helferich W. G., Hergenrother P. J., Nature Chem. Biol., 2006, 2, 543
[15] Peterson Q. P., Hsu D. C., Goode D. R., Novotny C. J., Totten R. K., Hergenrother P. J., J. Am. Chem. Soc., 2006, 128, 12424
[16] Peterson Q. P., Hsu D. C., Novotny C. J., West D. C., Kim D., Schmit J. M., Dirikolu L., Hergenrother P. J., Fan T. M., Cancer Res., 2010, 70, 7232
[17] Hsu D. C., Roth H. S., West D. C., Botham R. C., Novotny C. J. Schmid S. C., Hergenrother P. J., Comb. Sci., 2012, 14, 44
[18] West D. C., Qin Y., Peterson Q. P., Thomas D. L., Palchaudhuri R., Morrison K. C., Lucas P. W., Palmer A. E., Fan T. M., Hergenrother P. J., Mol. Pharmaceutics, 2012, 9, 1425
[19] Charkoudian L. K., Pham D. M., Franz K. J., J. Med. Chem., 2009, 52, 5721

Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

Design, Synthesis and Antitumor Activity of a Novel Series of PAC-1 Analogues

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 9

编辑推荐

Metrics

本文评价

[1]	TANG Xu, DU Zhijun, WU Guojie, HAN Fushe. Synthesis of P-Stereogenic Diarylphosphinamides as Novel Inhibitors of Melanoma[J]. 高等学校化学研究, 2019, 35(5): 812-816.
[2]	MA Junjie, HUANG Kun, NI Xin, CHEN Roufen, XU Boxuan, WANG Cuifang. Design, Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methyl b iphenyl Moiety[J]. 高等学校化学研究, 2019, 35(3): 410-417.
[3]	JIN Bo, TAO Ye, YANG Hongliang. Synthesis, Biological Evaluation and Molecular Docking of Novel Phenylpyrimidine Derivatives as Potential Anticancer Agents[J]. 高等学校化学研究, 2018, 34(6): 912-917.
[4]	ZHANG Lan, DENG Xinshan, WU Jiaofeng, MENG Guangpeng, LIU Congchong, CHEN Guzhou, ZHAO Qingchun, HU Chun. Design, Synthesis and Biological Activities of N-(Furan-2-ylmethyl)-1H-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents[J]. 高等学校化学研究, 2017, 33(3): 365-372.
[5]	LI Hongshuang, WU Xiaming, ZHANG Ruize, HAO Liqiang, DUAN Guiyun, XIAO Yuliang, XIA Chengcai, LI Furong, YOU Guirong, HAN Junfen. Synthesis and Biological Evaluation of Pyrano[2,3-f]chromene-4,8-dione Derivatives as Potential Anticancer Agents[J]. 高等学校化学研究, 2017, 33(2): 187-193.
[6]	YANG Hongliang, XU Guoxing, PEI Yazhong. Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents[J]. 高等学校化学研究, 2017, 33(1): 61-69.
[7]	HUANG Qiang, FU Qiangqiang, LIU Yajing, BAI Jinying, WANG Qianying, LIAO Huimin, GONG Ping. Design, Synthesis and Anticancer Activity of Novel 6-(Aminophenyl)-2,4-bismorpholino-1,3,5-triazine Derivatives Bearing Arylmethylene Hydrazine Moiety[J]. 高等学校化学研究, 2014, 30(2): 257-265.
[8]	MA Zheng-yue, ZHANG Xing-hua, LI Chun-na, ZHENG Ya-jun, YANG Geng-liang*, WANG S. Design and Synthesis of 3-Substituedmethylenethiochroman-4-ones as Anticancer Agents[J]. 高等学校化学研究, 2011, 27(5): 787-791.
[9]	TIAN Xuan, YANG Ming-gui, JI Zhu-sheng and CHEN Yao-zu, HE Xiao-qing, LEI Xiao-hong, HAN Rui. Anticancer Drugs (VI)——Synthesis and Activity of Spin Labeled Derivatives of 4-Amino-4-deoxy-4′-demethylepipodophyllotoxin[J]. 高等学校化学研究, 1996, 12(3): 304-308.