Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

doi:10.6023/cjoc201407042

Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (12): 2505-2510.DOI: 10.6023/cjoc201407042 Previous Articles Next Articles

ARTICLE

吡唑环桥连简约型长春碱类似物的设计合成

国翠平^a, 彭群龙^a, 潘龙^a, 张冬梅^a,b, 陈河如^a,b

a. 暨南大学药学院中药及天然药物研究所广州 510632;
b. 广东省中药药效物质基础及创新药物研究重点实验室广州 510632

收稿日期:2014-07-29 修回日期:2014-08-27 发布日期:2014-08-29
通讯作者: 陈河如 E-mail:thrchen@jnu.edu.cn
基金资助:
国家自然科学基金(No.81172982)资助项目.

Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

Guo Cuiping^a, Peng Qunlong^a, Pan Long^a, Zhang Dongmei^a,b, Chen Heru^a,b

a. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632;
b. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Guangzhou 510632

Received:2014-07-29 Revised:2014-08-27 Published:2014-08-29
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81172982).

A series of pyrazol-brigded simplified vinblastine analogues 2a～2m have been synthesized by the reaction of hydrazine derivatives with diformyl intermediates, which were prepared from 2,3,3-trimethyl-3H-indoles using P₂O₃Cl₄/DMF as Vilsmeier-Haack reagent. All the target compounds have been identified by ¹H NMR, ¹³C NMR and HRMS. The preliminary results of anticancer tests indicated that most of the compounds exhibit certain extent of anticancer activity against both MCF-7 (estrogen-positive) and HepG2 cell lines at the concentration of 50 μmol/L, respectively. 2f and 2j are the two best active compounds, where their cell viabilities against MCF-7 cell line are 28.0% and 21.4%, respectively; while against HepG2 cell line, 31.6% and 34.0%, respectively.

Key words: pharmacophore similarity, simplified design, vinca alkaloids analogues, antitumor, drug synthesis

Cite this article

Guo Cuiping, Peng Qunlong, Pan Long, Zhang Dongmei, Chen Heru. Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues[J]. Chin. J. Org. Chem., 2014, 34(12): 2505-2510.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Noble, R. L.; Beer, C. T.; Cutts, J. H. Ann. N. Y. Acad. Sci. 1958, 76, 882.
[2] Svoboda, G. H.; Neuss, N.; Gorman, M. J. J. Am. Pharm. Assoc. 1959, 48, 659.
[3] Dancey, J.; Steward, W. P. Anti-cancer Drugs 1995, 6, 625.
[4] (a) Langlois, N.; Gueritte, F.; Langlois, Y.; Potier, P. J. Am. Chem. Soc. 1976, 98, 7017. (b) Cros, S.; Wright, M.; Morimoto, M.; Lataste, H.; Couzinier, J. P.; Krikorian, A. Semin. Oncol. 1989, 16, 15.
[5] Sasaki, Y.; Kato, D.; Boger, D. L. J. Am. Chem. Soc. 2010, 132, 13533.
[6] Schleicher, K. D.; Sasaki, Y.; Tam, A. Kato, D.; Duncan, K. K.; Boger, D. L. J. Med. Chem. 2013, 56, 483.
[7] Keglevich, P.; Hazai, L.; Kalaus, G.; Szántay, C. Molecules 2012, 17, 5893.
[8] Ngo, Q. A.; Roussi, F.; Thoret, S.; Guéritte, F. Chem. Biol. Drug Des. 2010, 75, 284.
[9] Zheng, J.; Deng, L. J.; Chen, M. F.; Xiao, X. Z.; Xiao, S. W.; Guo, C. P.; Xiao, G. K.; Bai, L. L.; Ye, W. C.; Zhang, D. M.; Chen, H. R. Eur. J. Med. Chem. 2013, 65, 158.
[10] Baradarani, M. M.; Afghan, A.; Zebarjadi, F.; Hasanzadeh, K.; Joule, J. A. J. Heterocycl. Chem. 2006, 43, 1591.
[11] Rashidi, A.; Afghan, A.; Baradarani, M. M.; Joule, J. A. J. Heterocycl. Chem. 2009, 46, 428.
[12] Ye, J. H.; Ye, W. F.; Xiao, C. T.; Chen, Y.; Wang, G. P.; Zhang, W. Chin. J. Org. Chem. 2012, 32, 1503 (in Chinese). (叶家海, 叶文芳, 肖承涛, 陈雨, 王光普, 张文超, 有机化学, 2012, 32, 1503.)
[13] Kumar, V.; Kaur, K.; Karelia, D. N.; Beniwal, V.; Gupta, G. K.; Sharma, A. K.; Gupta, A. K. Eur. J. Med. Chem. 2014, 81, 267.
[14] Zhang, D. M.; Liu, J. S.; Tang, M. K.; Liu, A.; Cao, H. H.; Jiang, L.; Chan, J. Y.; Tian, H. Y.; Fung, K. P.; Ye, W. C. Eur. J. Pharmacol. 2012, 692, 19.
[15] Gigant, B.; Wang, C. G.; Ravelli, R. B. G.; Roussi, F.; Steinmetz, M. O.; Curmi, P. A.; Sobel, A.; Knossow, M. Nature 2005, 435, 519.

吡唑环桥连简约型长春碱类似物的设计合成

Design and Synthesis of Pyrazol-Bridged Simplified Vinblastine Analogues

PDF

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Guochao Liang, Tingting Dong, Haiying Ji, Chunyan Wang, Yali Song, Wei Zhang. Synthesis and Antitumor Activity of Novel 3,3'-((4-Chloro-2H-thiochromen-3-yl)methylene)bis(1H-indole)-Like Topoisomerase II Inhibitors [J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1949-1956.
[2]	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.
[3]	Panxing Pang, Rong Ning, Chuang Zhu, Wenjie Huang, Xianli Ma, Caina Jiang, Fangyao Li, Xiaoqun Zhou. Synthesis and in Vitro Antitumor Activity of Matrine Semicarbazide Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(6): 2126-2135.
[4]	Kanghui Duan, Junlong Tang, Wanqing Wu. Recent Advances in the Synthesis of Fused Heterocyclic Compounds and Their Antitumor Activities [J]. Chinese Journal of Organic Chemistry, 2023, 43(3): 826-854.
[5]	Chujie Liao, Hongyao Ruan, Junfeng Jiang, Lun Luo, Yanggen Hu. Synthesis and Activity Evaluation of 3-Aryl-2-imino-benzo[e][1,3]-oxazin-4-ol Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 763-770.
[6]	Weiqin Liu, Lihui Shao, Chengpeng Li, Yayu Zou, Haitao Long, Yan Li, Qiangsheng Ge, Zhenchao Wang, Guiping Ouyang. Synthesis and Antitumor Activity of 3-Hydrazone Quinazolinone Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 214-222.
[7]	Guangping Liang, Wei Wang, Xuxiu Zhu, Guangyan Liang, Jun Yang, Daoping Wang. Synthesis and in Vitro Anti-tumor Activity of Novel Spliced Compounds of Zidovudine and 4-Anilinoquinazolines [J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2793-2805.
[8]	Dongyan Hu, Guangtian Han, Xi'an Li, Huazhong Ren, Lirong Yue, Li Guo, Jiafu Feng. Synthesis and Evaluation in vitro of Novel Harmine Derivatives as Anticancer Activity Agents [J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1863-1871.
[9]	Lu Xue, Lihua Zhang, Chengyu Zhang, Xin Zhao, Weifan Dang, Zhaoxin Wang, Chunhua Wang, Tongchuan Suo, Xiaohui Yan. Discovery of Tiancimycin Congeners from Streptomyces sp. CB03234-S [J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1241-1247.
[10]	Siyu Zhu, Xinyu Huo, Qin Ma, Wei Chen, Jie Zhang, Liang Guo. Design, Synthesis, and Antitumor Activity of β-Carboline-Benzimidazole Hybrids [J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1129-1135.
[11]	Honglin Dai, Xiaojie Si, Lingling Chi, Hao Wang, Chao Gao, Zhengjie Wang, Limin Liu, Jiajie Ma, Fuqiang Yu, Hongmin Liu, Yu Ke, Qiurong Zhang. Synthesis and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Quinazoline Derivatives Containing Thiazole Structure [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3853-3862.
[12]	Zhengjie Wang, Honglin Dai, Xiaojie Si, Chao Gao, Limin Liu, Luye Zhang, Yang Zhang, Yadan Song, Peirong Zhao, Jiaxin Zheng, Yu Ke, Hongmin Liu, Qiurong Zhang. Synthesis and Antitumor Activity of 2,4,6-Trisubstituted Novel Quinazoline Derivatives Containing Trifluoromethyl [J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 249-256.
[13]	Lijun Yin, Chaoqun Li, Xiaoxia Wu, Guangsen Xu, Zhiying Li, Yuemao Shen. Synthesis of (E)-N-(4-Styrene) Acrylamides for DNA Topoisomerase IIα Inhibitors and Antitumor Agents [J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 293-301.
[14]	Jiaoli Ma, Penghu Guo, Jing Li, Xincheng Liao, Huicheng Cheng. Synthesis and Antitumor Activity of Amide Derivatives Containing 1,3,4-Thiadiazole and Pyrazole Moieties [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3214-3222.
[15]	Ningbo Li, Li Xu, Rong Ma, Qi Fan, Bo Li, Jie Qiao, Rui Guo, Xinhua Xu. Synthesis and Antitumor Activities of Novel Organic Sulfur (Selenium) Tegafur Derivatives [J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2723-2734.