Citation: Lin Zhiqing, Xia Wanling, Liu Renyi, Jiang Shaohua, Ma Zhiqiang. Synthesis of Cinnamic Acid-Coumarin Ester Analogs and Inhibition of Tyrosinase Activity[J]. Chinese Journal of Organic Chemistry, ;2020, 40(9): 2980-2987. doi: 10.6023/cjoc202005006 shu

Synthesis of Cinnamic Acid-Coumarin Ester Analogs and Inhibition of Tyrosinase Activity

Lin Zhiqing ^a ,
Xia Wanling ^a ,
Liu Renyi ^a ,
Jiang Shaohua ^a,, ,
Ma Zhiqiang ^a,b,,

a.
School of Biotechnology and Grand Health, Wuyi University, Jiangmen, Guangdong 529000
b.
School of Chemistry & Chemical Engineering, South China University of Technology, Guangzhou 510641

Corresponding author: Jiang Shaohua, wyuchemjsh@126.com Ma Zhiqiang, 23090330@qq.com
Received Date: 4 May 2020
Revised Date: 29 May 2020
Available Online: 19 June 2020
Fund Project: the Department of Education of Guangdong Province 19KZDXM035the Department of Education of Guangdong Province 2017KSYS010the Department of Education of Guangdong Province 2017KZDXM084Project supported by the Department of Education of Guangdong Province (Nos. 2017KSYS010, 2017KZDXM084, 2019KZDZX2003, 19KZDXM035)the Department of Education of Guangdong Province 2019KZDZX2003

Figures(4)

In medicinal chemistry, the structural modification of natural product and skeleton hybridization strategies is important way to improve the biological activity of template compound and find highly active lead compounds. In this work, two series of cinnamic acid-coumarin ester analogs were synthesized by using cinnamic acid and hydroxycoumarin as raw materials. And the tyrosinase inhibitory activity of the synthesized compounds was evaluated. The results indicated that the cinnamic acid-coumarin analogs had favourable tyrosinase inhibitory activity, especially 2-oxo-2H-benzopyran-4-yl(E)-3-(4-hydroxyphenyl)propenyl ester (C₈), 2-oxo-2H-benzopyran-7-yl(E)-3-(4-hydroxyphenyl)propenyl ester and (D₈) with IC₅₀ of (10.7±0.7) and (2.2±0.2) μmol·L^-1, respectively, which are 3 and 13 times that of kojic acid (IC₅₀ (28.5±1.1) μmol·L^-1). The structure-activity relationship analysis results showed that the introduction of substituents like F, Cl, and OH could efficiently enhance the tyrosinase inhibitory activity, and the inhibitory activity of condensation product of substituted cinnamic acid with 7-hydroxycoumarin was higher than that of substituted cinnamic acid with 4-hydroxycoumarin. Kinetic studies showed that the inhibitions of tyrosinase by compounds C₈ and D₈ are reversible mixed-type inhibitory effects. K_I values of C₈ and D₈ were 1.07 and 20.61 μmol·L^-1, respectively, and K_IS values were 3.72 and 27.09 μmol·L^-1, respectively. Finally, molecular docking was carried out to simulate the docking between compounds C₈ and D₈ with tyrosinase.
- tyrosinase,
- coumarin,
- cinnamic acid,
- molecular docking
1. [1]
  Xu, Y.; Lei, P.; Ling, Y.; Wang, S. W.; Yang X. L. Chin. J. Org. Chem. 2014, 34, 1118(in Chinese).
2. [2]
  Wu, L. D.; Rathi, B.; Chen, Y.; Wu, X. H.; Liu, H.; Li, J. C.; Ming, A. J.; Han, G. RSC Adv. 2018, 69, 39529.
3. [3]
  Rainer, B.; Revoltella, S.; Mayr, F.; Moesslacher, J.; Scalfari, V.; Kohl, R.; Waltenberger, B.; Pagitz, K.; Siewert, B.; Schwaiger, S.; Stuppner, H. Eur. J. Med. Chem. 2019, 184, 111738. doi: 10.1016/j.ejmech.2019.111738
4. [4]
  Rosada, B.; Bekier, A.; Cytarska, J.; Plazinski, W.; Zavyalova, O.; Sikora, A.; Dzitko, K.; Laczkowski, K. Z. Eur. J. Med. Chem. 2019, 184, 111765. doi: 10.1016/j.ejmech.2019.111765
5. [5]
  Chen, J. M.; Li, Q. L.; Ye, Y. L.; Huang, Z. Y.; Ruan, Z. P.; Jin, N. Spectrochim. Acta. A 2020, 226, 117642. doi: 10.1016/j.saa.2019.117642
6. [6]
  Lee, B.; Moon, K. M.; Lim, J. S.; Park, Y.; Kim, D. H.; Son, S.; Jeong, H. O.; Kim, D. H.; Lee, E. K.; Chung, K. W.; An, H. J.; Chun, P.; Seo, A. Y.; Yang, J. H.; Lee, B. S.; Ma, J. Y.; Cho, W. K.; Moon, H. R.; Chung, H. Y. Oncotarget 2017, 8, 91481. doi: 10.18632/oncotarget.20690
7. [7]
  Hwang, Y. S.; Oh, S. W.; Park, S. H.; Lee, J.; Yoo, J. A.; Kwon, K.; Park, S. J.; Kim, J.; Yu, E.; Cho, J. Y.; Lee, J. Oxid. Med. Cell. Longevity 2019, 9827519.
8. [8]
  Raza, H.; Abbasi, M. A.; Aziz-ur-Rehman.; Siddiqui, S. Z.; Hassan, M.; Abbas, Q.; Hong, H.; Shah, S. A. A.; Shahid, M.; Seo, S. Y. Bioorg. Chem. 2020, 94, 103445. doi: 10.1016/j.bioorg.2019.103445
9. [9]
  Cai, P. G.; Xiong, Y.; Yao, Y.; Chen, W.; Dong, X. W. New J. Chem. 2019, 43, 14102. doi: 10.1039/C9NJ02360G
10. [10]
  Pillaiyar, T.; Manickam, M.; Namasivayam, V. J. Enzyme Inhib. Med. Chem. 2017, 32, 403. doi: 10.1080/14756366.2016.1256882
11. [11]
  Ho, Y. S.; Wu, J. Y.; Chang, C. Y. Antioxidants 2019, 8, 474. doi: 10.3390/antiox8100474
12. [12]
  Arrowitz, C.; Schoelermann, A. M.; Mann, T.; Jiang, L. I.; Weber, T.; Kolbe, L. J. Invest. Dermatol. 2019, 139, 1691. doi: 10.1016/j.jid.2019.02.013
13. [13]
  Paudel, P.; Seong, S. H.; Wagle, A.; Min, B. S.; Jung, H. A.; Choi, J. S. Food Chem. 2020, 309, 125739. doi: 10.1016/j.foodchem.2019.125739
14. [14]
  Zhang, L.; Zhao, X.; Tao, G. J.; Chen, J.; Zheng, Z. P. Food Chem. 2017, 223, 40. doi: 10.1016/j.foodchem.2016.12.017
15. [15]
  Micheloni, O. B.; Farroni, A. E.; Garcia, P.; Furlan, R. L. E. Food Chem. 2018, 269, 638. doi: 10.1016/j.foodchem.2018.07.025
16. [16]
  Wang, R.; Chai, W. M.; Yang, Q.; Wei, M. K.; Peng, Y. Y. Bioorg. Med. Chem. 2016, 24, 4620. doi: 10.1016/j.bmc.2016.07.068
17. [17]
  Bhosle, M. R.; Khillare, L. D.; Mali, J. R.; Sarkate, A. P.; Lokwani, D. K.; Tiwari, S. V. New J. Chem. 2018, 42, 18621. doi: 10.1039/C8NJ04622K
18. [18]
  Dinparast, L.; Hemmati, S.; Zengin, G.; Alizadeh, A. A.; Bahadori, M. B.; Kafil, H. S.; Dastmalchi, S. ChemistrySelect 2019, 4, 9211. doi: 10.1002/slct.201901921
19. [19]
  Santi, M. D.; Bouzidi, C.; Gorod, N. S.; Puiatti, M.; Michel, S.; Grougnet, R.; Ortega, M. G. Bioorg. Chem. 2019, 82, 241. doi: 10.1016/j.bioorg.2018.10.034
20. [20]
  Saeedi, M.; Eslamifar, M.; Khezri, K. Biomed. Pharmacother. 2019, 110, 582. doi: 10.1016/j.biopha.2018.12.006
21. [21]
  Taofiq, O.; Heleno, S. A.; Calhelha, R. C.; Fernandes, I. P.; Alves, M. J.; Barros, L.; Gonzalez-Paramas, A. M.; Ferreira, I.; Barreiro, M. F. Microchem. J. 2019, 147, 469. doi: 10.1016/j.microc.2019.03.059
22. [22]
  Tavares-da-Silva, E. J.; Varela, C. L.; Pires, A. S.; Encarnacao, J. C.; Abrantes, A. M.; Botelho, M. F.; Carvalho, R. A.; Proenca, C.; Freitas, M.; Fernandes, E.; Roleira, F. M. F. Bioorg. Med. Chem. 2016, 24, 3556. doi: 10.1016/j.bmc.2016.05.065
23. [23]
  Zhao, Z. F.; Liu, G. X.; Meng, Y. F.; Tian, J. L.; Chen, X. F.; Shen, M. L.; Li, Y. X.; Li, B. Y.; Gao, C.; Wu, S. P.; Li, C. Q.; He, X. R.; Jiang, R.; Qian, M. C.; Zheng, X. H. Bioorg. Chem. 2019, 93, 103316. doi: 10.1016/j.bioorg.2019.103316
24. [24]
  Zhang, X. B.; Ma, H. Y.; Sun, T. D.; Lei, P.; Yang, X. L.; Zhang, X. M.; Ling, Y. Chin. J. Org. Chem. 2019, 39, 2965(in Chinese).
25. [25]
  Hussain, M. I.; Syed, Q. A.; Khattak, M. N. K.; Hafez, B.; Reigosa, M. J.; El-Keblawy, A. Biologia 2019, 74, 863. doi: 10.2478/s11756-019-00242-x
26. [26]
  Kurt, Z. B.; Sonmez, F.; Ozturk, D.; Akdemir, A; Angeli, A; Supuran, C. T. Eur. J. Med. Chem. 2019, 183, 111702. doi: 10.1016/j.ejmech.2019.111702
27. [27]
  Menezes, J. C. J. M. D. S.; Diederich, M. F. Eur. J. Med. Chem. 2019, 182, 111637. doi: 10.1016/j.ejmech.2019.111637
28. [28]
  Qiao, L. L.; Wei, Y.; Hao, S. H. Chin. J. Org. Chem. 2018, 38, 509(in Chinese).
29. [29]
  Xu, X. T.; Chen, J.; Lin, Z. Q.; Li, D. L.; Zhang, K.; Sheng, Z. J.; Wang, S. H.; Zhu, S.; Asiri, A. Chin. J. Org. Chem. 2019, 39, 2958(in Chinese).
30. [30]
  Wang, S. H.; Zhang, B. H.; Chen, J.; Zheng, Y. Y.; Feng, N.; Ma, A. J.; Xu, X. T.; Asiri, A. Chin. J. Org. Chem. 2020, 40, 15(in Chinese).
31. [31]
  Xu, L.; Wang, S. H.; Li, H. Chin. J. Org. Chem. 2015, 35, 1559(in Chinese).
32. [32]
  Xu, X. T.; Deng, X. Y.; Chen, J.; Liang, Q. M.; Zhang, K.; Li, D. L.; Wu, P. P.; Zheng, X.; Zhou, R. P.; Jiang, Z. Y.; Ma, A. J.; Chen, W. H.; Wang, S. H. Eur. J. Med. Chem. 2019, 189, 112013.
33. [33]
  Zhong, Y. Y.; Yu, L. J.; He, Q. Y.; Zhu, Q. Y.; Zhang, C. G.; Cui, X. P.; Zheng, J. X.; Zhao, S. Q. ACS Appl. Mater. Interfaces 2019, 11, 32769. doi: 10.1021/acsami.9b11754
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