Citation: Sun Haiyan, Sun Hongshun, Liu Mingzhen, Huang Wei, Yang Guangfu. Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure[J]. Chinese Journal of Organic Chemistry, ;2018, 38(8): 2067-2075. doi: 10.6023/cjoc201801001 shu

Lead Optimization and Antiproliferative Activity Using a New Dithiocarbamates Substructure

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

Corresponding author: Huang Wei, weihuangwuhan@126.com Yang Guangfu, gfyang@mail.ccnu.edu.cn
Received Date: 2 January 2018
Revised Date: 15 March 2018
Available Online: 13 August 2018
Fund Project: the Natural Science Foundation of Hubei Province 2016CFB562the National Natural Science Foundation of China 201502063Project supported by the National Natural Science Foundation of China (No. 201502063) and the Natural Science Foundation of Hubei Province (No. 2016CFB562)

Figures(4)

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.
- dithiocarbamate,
- quinazolinone,
- benzoxazinone,
- coumarin,
- antiproliferative activity
1. [1]
  Li, R.-D.; Wang, Y.-Q.; Ge, Z.-M.; Li, R.-T. Chin. J. Org. Chem. 2015, 35, 1805(in Chinese).
2. [2]
  Bala, V.; Gupta, G.; Sharma, V. L. Mini-Rev. Med. Chem. 2014, 14, 1021. doi: 10.2174/1389557514666141106130146
3. [3]
  Room, R.; Babor, T.; Rehm, J. Lancet 2005, 365, 519. doi: 10.1016/S0140-6736(05)70276-2
4. [4]
  Sauna, Z. E.; Shukla, S.; Ambudkar, S. V. Mol. Biosyst. 2005, 1, 127. doi: 10.1039/b504392a
5. [5]
  Schenk, H.; Klein, M.; Erdbrügger, W.; Dröge, W.; Schul-ze-Osthoff, K. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 1672. doi: 10.1073/pnas.91.5.1672
6. [6]
  Gaudernak, E.; Seipelt, J.; Triendl, A.; Grassauer, A.; Kuechler, E. J. Virol. 2002, 76, 6004. doi: 10.1128/JVI.76.12.6004-6015.2002
7. [7]
  Kraljević, T. G.; Harej, A.; Sedić, M.; Pavelić, S. K.; Stepanić, V.; Drenjančević, D.; Talapko, J.; Raić-Malić, S. Eur. J. Med. Chem. 2016, 124, 794. doi: 10.1016/j.ejmech.2016.08.062
8. [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).
9. [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. [10]
  Carta, F.; Aggarwal, M.; Maresca, A.; Scozzafava, A.; McKenna, R.; Masini, E.; Supuran, C. T. J. Med. Chem. 2012, 55, 1721. doi: 10.1021/jm300031j
11. [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. doi: 10.1016/j.bmc.2010.04.091
12. [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. doi: 10.1021/jm401002r
13. [13]
  Li, R. D.; Zhang, X.; Li, Q. Y.; Ge, Z. M.; Li, R. Bioorg. Med. Chem. Lett. 2011, 21, 3637. doi: 10.1016/j.bmcl.2011.04.096
14. [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. doi: 10.1159/000438620
15. [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. doi: 10.1016/j.bmc.2015.07.037
16. [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. doi: 10.1021/jm0508888
17. [17]
  Buac, D.; Schmitt, S.; Ventro, G.; Kona, F. R.; Dou, Q. P. Mini-Rev. in Med. Chem. 2012, 12, 1193. doi: 10.2174/138955712802762040
18. [18]
  Khan, I.; Zaib, S.; Batool, S.; Abbas, N.; Ashraf Z.; Iqbal, J.; Saeed, A. Bioorg. Med. Chem. 2016, 24, 2361. doi: 10.1016/j.bmc.2016.03.031
19. [19]
  Macías, F. A.; Marín, D.; Oliveros-Bastidas, A.; Molinillo, J. M. Nat. Prod. Rep. 2009, 26, 478. doi: 10.1039/b700682a
20. [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. doi: 10.1039/C4NP00162A
21. [21]
  Sandhu, S.; Bansal, Y.; Silakari, O.; Bansal, G. Bioorg. Med. Chem. 2014, 22, 3806. doi: 10.1016/j.bmc.2014.05.032
22. [22]
  Huang, W.; Ding, Y.; Miao, Y.; Yang, G. F. Eur. J. Med. Chem. 2009, 44, 3687. doi: 10.1016/j.ejmech.2009.04.004
23. [23]
  Huang, W.; Chen, Q.; Yang, W. C.; Yang, G. F. Eur. J. Med. Chem. 2013, 66, 161. doi: 10.1016/j.ejmech.2013.05.037
24. [24]
  Huang, W.; Liu, M. Z.; Li, Y.; Tan, Y.; Yang, G. F. Bioorg. Med. Chem. 2007, 15, 5191. doi: 10.1016/j.bmc.2007.05.022
25. [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). doi: 10.3321/j.issn:0253-2786.2004.10.027
26. [26]
  Clemence, F.; Le Martret, O.; Collard, J. J. Heterocycl. Chem. 1984, 21, 1345. doi: 10.1002/jhet.5570210520
27. [27]
  Leonetti, F.; Favia, A.; Rao, A.; Aliano, R.; Paluszcak, A.; Hartmann, R. W.; Carotti, A. J. Med. Chem. 2004, 27, 6792.
28. [28]
  Li, R. T.; Cai, M. S. Synth. Commun. 1998, 28, 295. doi: 10.1080/00397919808005722
29. [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 Gőttingen, Germany, 2001.
  (c) Bruker SMART V5. 628, SAINT V6. 45. & SADABS Bruker AXS Inc., Madison, Wisconsin, USA, 2001.
30. [30]
  Mosmann, T. J. Immunol. Methods 1983, 65, 55. doi: 10.1016/0022-1759(83)90303-4
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