Citation: Li Yang, Dong Shiyu, Qin Hongwei, Tang Bingyue, Gao Wentao, Chen Yu. A Facile Synthesis and M. tuberculosis Leucyl-tRNA Synthetase Inhi-bitory Activity of Novel 3-Arylvinylquinoxaline-2-carboxylic Acids[J]. Chinese Journal of Organic Chemistry, ;2020, 40(9): 2817-2826. doi: 10.6023/cjoc202001017 shu

A Facile Synthesis and M. tuberculosis Leucyl-tRNA Synthetase Inhi-bitory Activity of Novel 3-Arylvinylquinoxaline-2-carboxylic Acids

Li Yang ^a ,
Dong Shiyu ^a ,
Qin Hongwei ^a ,
Tang Bingyue ^a ,
Gao Wentao ^a,, ,
Chen Yu ^b,,

a.
College of Chemistry and Chemical Engineering, Bohai University, Jinzhou, Liaoning 121000
b.
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016

Corresponding author: Gao Wentao, bhuzh@163.com Chen Yu, isfc_bhu@yeah.net
Received Date: 11 January 2020
Revised Date: 28 May 2020
Available Online: 30 June 2020
Fund Project: the Doctoral Start-up Foundation of Liaoning Province 2019-BS-004the Scientific Research Foundation of the Education Department of Liaoning Province LQ2019006the National Natural Science Foundation of China 41602351the National Natural Science Foundation of China U1608222Project supported by the National Natural Science Foundation of China (Nos. 21878023, U1608222, 41602351), the Doctoral Start-up Foundation of Liaoning Province (No. 2019-BS-004) and the Scientific Research Foundation of the Education Department of Liaoning Province (No. LQ2019006)the National Natural Science Foundation of China 21878023

Figures(5)

In the present work, a simple and facile synthesis of a new series of 3-arylvinylquinoxaline-2-carboxylic acids has been achieved using the newly-synthesized ethyl 3-bromomethylquinoxaline-2-carboxylate as substrate through one-pot sequential Arbuzov/Horner-Wadsworth-Emmons (HWE)/ester hydrolysis reaction procedure. A primary in vitro evaluation for their inhibitory activity against Mycobacterium smegmatis (M. smegmatis) Leucyl-tRNA synthetase (Mtb LeuRS) revealed that (E)-3-(3-nitrostyryl)quinoxaline-2-carboxylic acid (5j) represented the most active compound in this round of effort with the IC₅₀ value of 14.7 μmol·L^-1, which was much superior to the reference drug AN2679, indicating the potential medicinal value for the exploration of novel Mtb LeuRS inhibitor. The results of molecular docking analyses using CDOCKER module of Discovery Studio (DS) software suggested that it could bind well to the active site of Mtb LeuRS. Moreover, the antitubercular assay against M. smegmatis also revealed that the nitro-substituted 5j has the best anti-tubercular activity with the minimum inhibitory concentration (MIC) value 15.6 μg/mL, being comparable with the reference rifampicin.
- quinoxaline,
- bromination reaction,
- one-pot three-step,
- M. smegmatis,
- Leucyl-tRNA synthetase
1. [1]
  World Health Organization Global Tuberculosis Report 2019, World Health Organization, Geneva, 2019, http://www.who.int/tb/publications/global_report/en/
2. [2]
  Chan, E. D.; Iseman, M. D. Curr. Opin. Infect. Dis. 2008, 21, 587. doi: 10.1097/QCO.0b013e328319bce6
3. [3]
  Gudzera, O. I.; Golub, A. G.; Bdzhola, V. G.; Volynets, G. P.; Kovalenko, O. P.; Boyarshin, K. S.; Yaremchuk, A. D.; Protopopov, M. V.; Yarmoluk, S. M.; Tukalo, M. A. J. Enzyme Inhib. Med. Chem. Chem. 2016, 31, 201. doi: 10.1080/14756366.2016.1190712
4. [4]
  Lee, S. W.; Choi, E. C.; Choi, S. Y. Appl. Microbiol. Biotechnol. 2003, 61, 278. doi: 10.1007/s00253-003-1243-5
5. [5]
  Ding, D.; Meng, Q.; Gao, G.; Zhao, Y.; Wang, Q.; Nare, B.; Jacobs, R.; Rock, F.; Alley, M. R. K.; Plattner, J. J.; Chen, G.; Li, D.; Zhou, H. J. Med. Chem. 2011, 54, 1276. doi: 10.1021/jm101225g
6. [6]
  Zhang, F.; Du, J.; Wang, Q.; Hu, Q.; Zhang, J.; Ding, D.; Zhao, Y.; Yang, F.; Wang, E.; Zhou, H. Org. Biomol. Chem. 2013, 11, 5310. doi: 10.1039/c3ob40236c
7. [7]
  Bernier, S.; Akochy, P.-M.; Lapointe, J.; Chênevert, R. Bioorg. Med. Chem. 2005, 13, 69. doi: 10.1016/j.bmc.2004.09.055
8. [8]
  Li, X.; Hernandez, V.; Rock, F. L.; Choi, W.; Mak, Y. S. L.; Mohan, M.; Mao, W.; Zhou, Y.; Easom, E. E.; Plattner, J. J.; Zou, W.; Pérez-Herrán, E.; Giordano, I.; Mendoza-Losana, A.; Alemparte, C.; Rullas, J.; Angulo-Barturen, I.; Crouch, S.; Ortega, F.; Barros, D.; Alley, M. R. K. J. Med. Chem. 2017, 60, 8011. doi: 10.1021/acs.jmedchem.7b00631
9. [9]
  Gudzera, O. I.; Golub, A. G.; Bdzhola, V. G.; Volynets, G. P.; Lukashov, S. S.; Kovalenko, O. P.; Kriklivyi, I. A.; Yaremchuk, A. D.; Starosyla, S. A.; Yarmoluk, S. M.; Tukalo, M. A. Bioorg. Med. Chem. 2016, 24, 1023. doi: 10.1016/j.bmc.2016.01.028
10. [10]
  Zhang, P.; Ma, S. Med. Chem. Commun. 2019, 10, 1329. doi: 10.1039/C9MD00139E
11. [11]
  Montana, M.; Mathias, F.; Terme, T.; Vanelle, P. Eur. J. Med. Chem. 2019, 163, 136. doi: 10.1016/j.ejmech.2018.11.059
12. [12]
  Cong, W. X.; Wang, L.; Yu, F. Q.; Li, J. X. Chin. J. Org. Chem. 2018, 38, 2866(in Chinese).
13. [13]
  Ajani, O. O. Eur. J. Med. Chem. 2014, 85, 688. doi: 10.1016/j.ejmech.2014.08.034
14. [14]
  Tariq, S.; Somakala, K.; Amir, M. Eur. J. Med. Chem. 2018, 143, 542. doi: 10.1016/j.ejmech.2017.11.064
15. [15]
  Santivañez-Veliz, M.; Pérez-Silanes, S.; Torres, E.; Moreno-Viguri, E. Bioorg. Med. Chem. Lett. 2016, 26, 2188. doi: 10.1016/j.bmcl.2016.03.066
16. [16]
  Ancizu, S.; Moreno, E.; Solano, B.; Villar, R.; Burguete, A.; Torres, E.; Pérez-Silanes, S.; Aldana, I.; Monge, A. Bioorg. Med. Chem. 2010, 18, 2713. doi: 10.1016/j.bmc.2010.02.024
17. [17]
  Puratchikody, A.; Natarajan, R.; Jayapal, M.; Doble, M. Chem. Biol. Drug Des. 2011, 78, 988. doi: 10.1111/j.1747-0285.2011.01246.x
18. [18]
  Kumar, K. S.; Rambabu, D.; Sandra, S.; Kapavarapu, R.; Krishna, G. R.; Rao, M. V. B.; Chatti, K.; Reddy, C. M.; Misra, P.; Pal, M. Bioorg. Med. Chem. 2012, 20, 1711. doi: 10.1016/j.bmc.2012.01.012
19. [19]
  Seitz, L. E.; Suling, W. J.; Reynolds, R. C. J. Med. Chem. 2002, 45, 5604. doi: 10.1021/jm020310n
20. [20]
  Magnet, S.; Hartkoorn, R. C.; Székely, R.; Pató, J.; Triccas, J. A.; Schneider, P.; Szántai-Kis, C.; Orfi, L.; Chambon, M.; Banfi, D.; Bueno, M.; Turcatti, G.; Kéri, G.; Cole, S. T. Tuberculosis 2010, 90, 354. doi: 10.1016/j.tube.2010.09.001
21. [21]
  Mekouar, K.; Mouscadet, J.-F.; Desmaële, D.; Subra, F.; Leh, H.; Savouré, D.; Auclair, C.; d'Angelo, J. J. Med. Chem. 1998, 41, 2846. doi: 10.1021/jm980043e
22. [22]
  Dai, H.; Ding, Y.; Du, X. C.; Yao, W.; Chen, Q. W.; Wang, X. L.; Zhong, S. L.; Cao, X. F.; Shi, Y. J. Chin. J. Org. Chem. 2018, 38, 1755(in Chinese).
23. [23]
  Wei, Q.; Li, J.; Tang, F.; Yin, Y.; Zhao, Y.; Yao, Q. Eur. J. Med. Chem. 2018, 144, 504. doi: 10.1016/j.ejmech.2017.12.008
24. [24]
  He, H.; Ge, Y.; Dai, H.; Cui, S.; Ye, F.; Jin, J.; Shi, Y. Molecules 2016, 21, 1722. doi: 10.3390/molecules21121722
25. [25]
  Shingalapur, R. V.; Hosamani, K. M.; Keri, R. S. Eur. J. Med. Chem. 2009, 44, 4244. doi: 10.1016/j.ejmech.2009.05.021
26. [26]
  Jadhavar, P. S.; Dhameliya, T. M.; Vaja, M. D.; Kumar, D.; Sridevi, J. P.; Yogeeswari, P.; Sriram, D.; Chakraborti, A. K. Bioorg. Med. Chem. Lett. 2016, 26, 2663. doi: 10.1016/j.bmcl.2016.04.012
27. [27]
  De, P.; Veau, D.; Belval, F. B.; Chassaing, S.; Baltas, M. Cinnamic Derivatives in Tuberculosis, In Understanding Tuberculosis-New Approaches to Fighting Against Drug Resistance, Ed.: Cardona, P.-J., ISBN: 978-953-307-948-6, In Tech., 2012.
28. [28]
  Fan, Y.; Wu, J.; Cheng, X.; Zhang, F.; Feng, L. Eur. J. Med. Chem. 2018, 146, 554. doi: 10.1016/j.ejmech.2018.01.080
29. [29]
  Lu, X.; Wan, B.; Franzblau, S. G.; You, Q. Eur. J. Med. Chem. 2011, 46, 3551. doi: 10.1016/j.ejmech.2011.05.018
30. [30]
  Maresca, A.; Vullo, D.; Scozzafava, A.; Manole, G.; Supuran, C. T. J. Enzym. Inhib. Med. Chem. 2013, 28, 392. doi: 10.3109/14756366.2011.650168
31. [31]
  Chang, F.-S.; Chen, W.; Wang, C.; Tzeng, C.-C.; Chen, Y.-L. Bioorg. Med. Chem. 2010, 18, 124. doi: 10.1016/j.bmc.2009.11.012
32. [32]
  Kumar, B. S. P. A.; Madhav, B.; Reddy, K. H. V.; Nageswar, Y. V. D. Tetrahedron Lett. 2011, 52, 2862. doi: 10.1016/j.tetlet.2011.03.110
33. [33]
  Gong, L.; Xing, L. J.; Xu, T.; Zhu, X. P.; Zhou, W.; Kang, N.; Wang, B. Org. Biomol. Chem. 2014, 12, 6557. doi: 10.1039/C4OB01025F
34. [34]
  Kamal, A.; Rahim, A.; Riyaz, S.; Poornachandra, Y.; Balakrishna, M.; Kumar, C. G.; Hussaini, S. M. A.; Sridhar, B.; Machiraju, P. K. Org. Biomol. Chem. 2015, 13, 1347. doi: 10.1039/C4OB02277G
35. [35]
  Sharma, R.; Abdullaha, M.; Bharate, S. B. J. Org. Chem. 2017, 82, 9786. doi: 10.1021/acs.joc.7b00856
36. [36]
  Achelle, S.; Barsella, A.; Baudequin, C.; Caro, B.; Guen, F. R. J. Org. Chem. 2012, 77, 4087. doi: 10.1021/jo3004919
37. [37]
  Carbon, J. A. J. Org. Chem. 1960, 25, 1731. doi: 10.1021/jo01080a013
38. [38]
  Xu, J.; Zhang, L. H.; Zhang, M. Q.; Liu, X. B.; Ma, W.; Tang, Y. X.; Wang, D. L. Chin. J. Org. Chem. 2019, 39, 2808(in Chinese).
39. [39]
  Li, Y.; Tang, B. Y.; Dong, S. Y.; Gao, W. T.; Jiang, W. T.; Chen, Y. ChemistrySelect 2020, 5, 2746. doi: 10.1002/slct.201904434
40. [40]
  Li, Y.; Xu, Q. Q.; Li, Z. Y.; Gao, W. T.; Chen, Y. Mol. Diversity 2020, 24, 167. doi: 10.1007/s11030-019-09938-3
41. [41]
  Thapa, R.; Brown, J.; Balestri, T.; Brown, J.; Taylor, R. T. Tetrahedron Lett. 2014, 55, 6743. doi: 10.1016/j.tetlet.2014.08.069
42. [42]
  Zhong, K. L.; Zhao, J.; Li, Q. Y.; Hou, S. H.; Tang, Y. W.; Bian, Y. J.; Tang, L. J. Chin. J. Org. Chem. 2018, 38, 1786(in Chinese).
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