Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure

doi:10.6023/cjoc201801001

Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (8): 2067-2075.DOI: 10.6023/cjoc201801001 Previous Articles Next Articles

Articles

基于二硫代氨基甲酸酯活性亚结构的先导优化及其抗增殖活性

孙海燕^a, 孙宏顺^a, 刘明珍^b, 黄伟^b, 杨光富^b

a 南京科技职业学院南京 210048;
b 华中师范大学化学学院农药与化学生物学教育部重点实验室武汉 430079

收稿日期:2018-01-02 修回日期:2018-03-15 发布日期:2018-04-13
通讯作者: 黄伟, 杨光富 E-mail:weihuangwuhan@126.com;gfyang@mail.ccnu.edu.cn
基金资助:
国家自然科学基金（No.201502063）、湖北省自然科学基金（No.2016CFB562）资助项目.

Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure

Sun Haiyan^a, Sun Hongshun^a, Liu Mingzhen^b, Huang Wei^b, Yang Guangfu^b

a Nanjing Polytechnic Institute, Nanjing 210048;
b Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079

Received:2018-01-02 Revised:2018-03-15 Published:2018-04-13
Contact: 10.6023/cjoc201801001 E-mail:weihuangwuhan@126.com;gfyang@mail.ccnu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (No. 201502063) and the Natural Science Foundation of Hubei Province (No. 2016CFB562).

1. Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure.PDF(2567KB)

Abstract

In this work, a series of dithiocarbamate derivatives bearing diverse quinazolinones, benzoxazinones, and coumarin moieties were designed and synthesized via a one-pot three-component reaction. These compounds produced good yields and functioned quickly under mild conditions, and the desired products were readily isolated. Their in vitro antitumor activities were evaluated by the methyl thiazolyl tetrazolium (MTT) method against hepatoma carcinoma cells HCCLM-7, cervical carcinoma cells Hela, mammary adenocarcinoma cells MDA-MB-435S, colon carcinoma cells SW-480, laryngocarcinoma cells Hep-2, and mammary adenocarcinoma cells MCF-7. 3 compounds were identified as the most promising candidates, due to their high potency and broad-spectrum antiproliferative activity (IC₅₀:3.5~13.5 μmol·L^-1). The activities of some lead compounds were more than 10-fold more potent than that of positive control 5-fluorouracil (5-FU) (IC₅₀:8.1~128.7 μmol·L^-1). These results indicated that the dithiocarbamate (DTC) derivatives bearing fused heterocyclic moieties could be used as lead for further developing new antitumor active compounds.

Key words: dithiocarbamate, quinazolinone, benzoxazinone, coumarin, antiproliferative activity

Cite this article

Sun Haiyan, Sun Hongshun, Liu Mingzhen, Huang Wei, Yang Guangfu. Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure[J]. Chin. J. Org. Chem., 2018, 38(8): 2067-2075.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Li, R.-D.; Wang, Y.-Q.; Ge, Z.-M.; Li, R.-T. Chin. J. Org. Chem. 2015, 35, 1805(in Chinese). (李日东, 王元强, 葛泽梅, 李润涛有机化学, 2015, 35, 1805.)
[2] Bala, V.; Gupta, G.; Sharma, V. L. Mini-Rev. Med. Chem. 2014, 14, 1021.
[3] Room, R.; Babor, T.; Rehm, J. Lancet 2005, 365, 519.
[4] Sauna, Z. E.; Shukla, S.; Ambudkar, S. V. Mol. Biosyst. 2005, 1, 127.
[5] Schenk, H.; Klein, M.; Erdbrügger, W.; Dröge, W.; Schul-ze-Osthoff, K. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 1672.
[6] Gaudernak, E.; Seipelt, J.; Triendl, A.; Grassauer, A.; Kuechler, E. J. Virol. 2002, 76, 6004.
[7] Kraljevic, T. G.; Harej, A.; Sedic, M.; Pavelic, S. K.; Stepanic, V.; Drenjancevic, D.; Talapko, J.; Raic-Malic, S. Eur. J. Med. Chem. 2016, 124, 794.
[8] Mo, S.; Ding, Y.; Zhang, G.; Zhang, Z.; Shao, X.-B.; Li, Q.-Y.; Yang, X.-J.; Chen, F. Chin. J. Org. Chem. 2017, 37, 1000(in Chinese). (莫松, 丁勇, 张刚, 张震, 杓学蓓, 李清寒, 杨学军, 陈峰, 有机化学, 2017, 37, 1000.)
[9] (a) Fu, D. J.; Zhang, S. Y.; Liu, Y. C.; Zhang, L.; Liu, J. J.; Song, J.; Zhao, R. H.; Li, F.; Sun H. H.; Liu, H. M.; Zhang, Y. B. Bioorg. Med. Chem. Lett. 2016, 26, 3918.
(b) Ding, P. P.; Gao, M.; Mao, B. B.; Cao, S. L.; Liu, C. H.; Yang, C. R.; Li, Z. F.; Liao, J.; Zhao, H. C.; Li, Z. Eur. J. Med. Chem. 2016, 108, 364.
(c) Fu, D. J.; Zhang, L.; Song, J.; Mao, R. W.; Zhao, R. H.; Liu, Y. C.; Hou, Y. H.; Li, J. H.; Yang J. J.; Jin, C. Y.; Li, P.; Zi, X. L.; Liu, H. M.; Zhang, S. Y.; Zhang, Y. B. Eur. J. Med. Chem. 2017, 127, 87.
(d) Jian, F.-F.; Xu, L.-Z.; Wen, L.-R.; Zhu, C.-Y. Chin. J. Org. Chem. 2005, 25, 423(in Chinese). (建方方, 许良忠, 文丽荣, 朱崇毅, 有机化学, 2005, 25, 423.)
[10] Carta, F.; Aggarwal, M.; Maresca, A.; Scozzafava, A.; McKenna, R.; Masini, E.; Supuran, C. T. J. Med. Chem. 2012, 55, 1721.
[11] Qian, Y.; Ma, G. Y.; Yang, Y.; Chen, K.; Zheng, Q. Z.; Mao, W. J.; Shi, L.; Zhao, J.; Zhu, H. L. Bioorg. Med. Chem. 2010, 18, 4310.
[12] Zheng, Y. C.; Duan, Y. C.; Ma, J. L.; Xu, R. M.; Zi, X.; Lv, W. L.; Wang, M. M.; Ye, X. W.; Zhu, S.; Mobley, D.; Zhu, Y. Y.; Wang, J. W.; Li, J. F.; Wang, Z. R.; Zhao, W.; Liu, H. M. J. Med. Chem. 2013, 56, 8543.
[13] Li, R. D.; Zhang, X.; Li, Q. Y.; Ge, Z. M.; Li, R. Bioorg. Med. Chem. Lett. 2011, 21, 3637.
[14] Zheng, Y. C.; Wang, L. Z.; Zhao, L. J.; Zhao, L. J.; Zhan, Q. N.; Ma, J. L.; Zhang, B.; Wang, M. M.; Wang, Z. R.; Li, J. F.; Liu, Y.; Chen, Z. S.; Shen, D. D.; Liu, X. Q.; Ren, M.; Lv, W. L.; Zhao, W.; Duan, Y. C.; Liu, H. M. Cell. Physiol. Biochem. 2016, 38, 185.
[15] Kamal, A.; Sathish. M., N ayak, V. L.; Srinivasulu, V.; Kavitha, B.; Tangella, Y.; Thummuri, D.; Bagul, C.; Shankaraiah, N., N agesh, N. Bioorg. Med. Chem. 2015, 23, 5511.
[16] Gaspari, P.; Banerjee, T.; Malachowski, W. P.; Muller, A. J.; Prendergast, G. C.; DuHadaway, J.; Bennett, S.; Donovan, A. M. J. Med. Chem. 2006, 49, 684.
[17] Buac, D.; Schmitt, S.; Ventro, G.; Kona, F. R.; Dou, Q. P. Mini-Rev. in Med. Chem. 2012, 12, 1193.
[18] Khan, I.; Zaib, S.; Batool, S.; Abbas, N.; Ashraf Z.; Iqbal, J.; Saeed, A. Bioorg. Med. Chem. 2016, 24, 2361.
[19] Macías, F. A.; Marín, D.; Oliveros-Bastidas, A.; Molinillo, J. M. Nat. Prod. Rep. 2009, 26, 478.
[20] Medina, F. G.; Marrero, J. G.; Macías-Alonso, M.; González, M. C.; Córdova-Guerrero, I.; Teissier García, A. G.; Osegueda-Robles, S. Nat. Prod. Rep. 2015, 32, 1472.
[21] Sandhu, S.; Bansal, Y.; Silakari, O.; Bansal, G. Bioorg. Med. Chem. 2014, 22, 3806.
[22] Huang, W.; Ding, Y.; Miao, Y.; Yang, G. F. Eur. J. Med. Chem. 2009, 44, 3687.
[23] Huang, W.; Chen, Q.; Yang, W. C.; Yang, G. F. Eur. J. Med. Chem. 2013, 66, 161.
[24] Huang, W.; Liu, M. Z.; Li, Y.; Tan, Y.; Yang, G. F. Bioorg. Med. Chem. 2007, 15, 5191.
[25] Liu, G.; Song, B. A.; Sang, W. J.; Yang, S.; Jin, L. H.; Ding, X. Chin. J. Org. Chem. 2004, 24, 1296(in Chinese). (刘刚, 宋宝安, 桑维钧, 杨松, 金林红, 丁雄, 有机化学, 2004, 24, 1296.)
[26] Clemence, F.; Le Martret, O.; Collard, J. J. Heterocycl. Chem. 1984, 21, 1345.
[27] Leonetti, F.; Favia, A.; Rao, A.; Aliano, R.; Paluszcak, A.; Hartmann, R. W.; Carotti, A. J. Med. Chem. 2004, 27, 6792.
[28] Li, R. T.; Cai, M. S. Synth. Commun. 1998, 28, 295.
[29] (a) Full crystallographic details has been deposited at the Cambridge Crystallographic Data Center and allocated the deposition number CCDC 715987(2h).
(b) Sheldrick, G. M. SHELXTL (Version 5. 0), University of Gottingen, Germany, 2001.
(c) Bruker SMART V5.628, SAINT V6.45. & SADABS Bruker AXS Inc., Madison, Wisconsin, USA, 2001.
[30] Mosmann, T. J. Immunol. Methods 1983, 65, 55.

基于二硫代氨基甲酸酯活性亚结构的先导优化及其抗增殖活性

Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	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.
[2]	Ran Zhou, Chunmei Yuan, Tao Zhang, Piao Mao, Yi Liu, Kaini Meng, Hui Xin, Wei Xue. Design, Synthesis and Bioactivity of Chalcone Derivative Containing Quinazolinone [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3196-3209.
[3]	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.
[4]	Lei Wang, Shujing Yu, Na Yang, Baolei Wang. Studies on the Synthesis and Biological Activities of Novel Dihydroquinazolinone-Containing Caffeine Derivatives [J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 299-307.
[5]	Jiling Yi, Kangqi Shi, Binglin Wu, Wanshan Li, Guangying Chen. Study on Secondary Metabolites of Marine-Derived Fungus Eutypella sp. F0219 [J]. Chinese Journal of Organic Chemistry, 2023, 43(1): 295-298.
[6]	Zhentao Pan, Tong Liu, Yongmin Ma, Jianbo Yan, Ya-Jun Wang. Construction of Quinazolin(thi)ones by Brønsted Acid/Visible-Light Photoredox Relay Catalysis [J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2823-2831.
[7]	Wei Chen, Simin Lei, Yuxin Lan, Haojian Xu, Pingbin Yu, Rui Zhang, Run Wu, Yang Chen. Design, Synthesis and Antifungal Activities of Novel Quinazolinone Derivatives [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2164-2171.
[8]	Chao Gao, Xiaojie Si, Lingling Chi, Hao Wang, Honglin Dai, Limin Liu, Zhengjie Wang, Yang Zhang, Tao Wang, Yaochuan Zhou, Jiaxin Zheng, Yu Ke, Hongmin Liu, Qiurong Zhang. Synthesis and Antiproliferative Activity of 2,4,5,6-Tetrasubstituted Pyrimidine Derivatives Containing Anisole [J]. Chinese Journal of Organic Chemistry, 2022, 42(6): 1677-1686.
[9]	Ruiqin Zhang, Renchao Ma, Qinjiao Fu, Jing Chen, Yongmin Ma. I₂/PhNO₂ Mediated Synthesis of Quinazolin-4(3H)-ones by C(CO)—C Bond Oxidative Cleavage of Acetophenones and Amination with 2-Aminobenzamides [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 854-862.
[10]	Yudong Li, Ying Li, Ya'nan Dong, Chungu Xia, Yuehui Li. Manganese-Catalyzed Allylation of Quinazolinones with 4-Vinyl-1,3-dioxolan-2-one via C—H Activation [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 847-853.
[11]	Mianyuan Wu, Yanchao Yu, Yang Liu, Jun You, Wenju Wu, Bo Liu. Synthesis and Application of a Novel Fluorescent Probe for Sequential Recognition Cu²⁺ and Glyphosate [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 803-811.
[12]	Yaquan Cao, Yingxue Yang, Hongjin Zhai, Jin Wang, Shuo Zhang, Huanhuan Wang, Pu Yang, Chunli Wu. Synthesis and Antitumor Activity of Novel 5- and 6-Substituted Indazole Derivatives [J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 590-599.
[13]	Yamin Sun, Xiyong Li, Jinwei Yuan, Jialin Yu, Shuainan Liu. CuI-Catalyzed Regioselective Synthesis of 3-Arylcoumarins with Arylamines under Mild Conditions [J]. Chinese Journal of Organic Chemistry, 2022, 42(2): 631-640.
[14]	Tao Zhang, Haiyuan Wei, Wen Ma, Zhangyuan Li, Panpan Hu, Nanqian Zhou, Jianchao He, Ting Li, Mingming Su, Suping Bai. Synthesis and Antiproliferative Activity Evaluation of Novel Glaucocalyxin A-1,2,3-Triazole Derivatives [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3668-3683.
[15]	Mingzhou Shang, Lanlan Zhang, Miaomiao Chen, Wangcheng Hu, Xinwei He, Hongjian Lu. Synthesis of Esterified/Fused Isocoumarins via Rh-Catalyzed C—H Activation/Transannulative Coupling/Annulation of Phthalic Anhydrides with Cyclic 2-Diazo-1,3-diketones and Methanol [J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3816-3823.