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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Research Article

Design, Synthesis and Biological Evaluation of Nucleozin Sulfonyl Piperazine Derivatives as Anti-influenza A Virus Inhibitors

Author(s): Shuchen Pei, Junlin Chen, Jinhua Yang, Lin Lai, Xiang Huang, Mingxin Xu and Jun Chen*

Volume 20, Issue 6, 2023

Published on: 20 October, 2022

Page: [501 - 506] Pages: 6

DOI: 10.2174/1570178619666220919102545

Price: $65

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Abstract

Influenza A viruses have caused worldwide epidemics and pandemics by reassortment and generation of drug-resistant mutants, which leads to an urgent need to develop novel antivirals. In this study, a series of sulfonyl piperazine nucleozin derivatives were designed and synthesized, and their in vitro anti-influenza activity was evaluated. Many of these compounds exhibited moderate to good anti-influenza activity against influenza A. Among these, 6d, 6g, 6h, 6i, and 6j exhibited better activity than ribavirin. 2,3-dichlorobenzene substituted analogue 6i displayed the most remarkable in vitro activity against Influenza A. All the derivatives show no obvious cellular growth inhibition against MDCK cells. This study reported a new series of nucleoprotein inhibitors with a good selectivity window and potential for further development as novel anti-influenza agents.

Keywords: Anti-influenza A, nucleoprotein, sulfonyl piperazine derivatives, drug design, synthesis, biological evaluation.

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[1]
Wang, G.; Wan, J.; Hu, Y.; Wu, X.; Prhavc, M.; Dyatkina, N.; Rajwanshi, V.K.; Smith, D.B.; Jekle, A.; Kinkade, A.; Symons, J.A.; Jin, Z.; Deval, J.; Zhang, Q.; Tam, Y.; Chanda, S.; Blatt, L.; Beigelman, L. J. Med. Chem., 2016, 59(10), 4611-4624.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01933] [PMID: 27120583]
[2]
Moore, K.A.; Ostrowsky, J.T.; Kraigsley, A.M.; Mehr, A.J.; Bresee, J.S.; Friede, M.H.; Gellin, B.G.; Golding, J.P.; Hart, P.J.; Moen, A.; Weller, C.L.; Osterholm, M.T.; Ampofo, W.; Barclay, W.; Cavaleri, M.; Cohen, C.; Cowling, B.; Cox, R.; Gust, I.; Innis, B.; Kang, G.; Katz, J.; Krammer, F.; Pitisuttithum, P.; Post, D.; Rudenko, L.; Siqueira, M.; Weir, J. Vaccine, 2021, 39(45), 6573-6584.
[http://dx.doi.org/10.1016/j.vaccine.2021.08.010] [PMID: 34602302]
[3]
Lytle, K.L.; Collins, S.P.; Feldstein, L.R.; Baughman, A.H.; Brown, S.M.; Casey, J.D.; Erickson, H.L.; Exline, M.C.; Files, D.C.; Gibbs, K.W.; Ginde, A.A.; Gong, M.N.; Grijalva, C.G.; Khan, A.; Lindsell, C.J.; Peltan, I.D.; Prekker, M.E.; Rice, T.W.; Shapiro, N.I.; Steingrub, J.S.; Stubblefield, W.B.; Tenforde, M.W.; Womack, K.N.; Patel, M.M.; Self, W.H. Vaccine, 2021, 39(37), 5271-5276.
[http://dx.doi.org/10.1016/j.vaccine.2021.07.057] [PMID: 34376307]
[4]
Takashita, E.; Abe, T.; Morita, H.; Nagata, S.; Fujisaki, S.; Miura, H.; Shirakura, M.; Kishida, N.; Nakamura, K.; Kuwahara, T.; Mitamura, K.; Ichikawa, M.; Yamazaki, M.; Watanabe, S.; Hasegawa, H.; Komagome, R.; Ohnishi, A.; Tsutsui, R.; Takahashi, M.; Sasaki, M.; Tamura, S.; Shibata, C.; Komabayashi, K.; Saito, N.; Saito, A.; Mizukoshi, F.; Wakatsuki, A.; Tsukagoshi, H.; Suzuki, N.; Uno, Y.; Oitate, N.; Nishikawa, W.; Nagashima, M.; Watanabe, S.; Kawakami, C.; Shimizu, H.; Amano, H.; Kanazawa, S.; Watanabe, K.; Yamamoto, K.; Yoneda, T.; Nakamura, S.; Sato, K.; Oonuma, M.; Takeuchi, M.; Tanaka, E.; Nishioka, M.; Sato, Y.; Sakai, Y.; Maehata, T.; Furuta, T.; Yasui, Y.; Yano, T.; Tanino, A.; Hirata, S.; Nagasao, A.; Hiroi, S.; Kubo, H.; Okayama, F.; Oshibe, T.; Mori, A.; Murayama, R.; Chiba, S.; Matsui, Y.; Kiguchi, Y.; Takeuchi, K.; Mita, T.; Nomiya, K.; Shimazu, Y.; Fujii, Y.; Toda, S.; Kawakami, Y.; Terajima, Y.; Yamashita, M.; Takahashi, T.; Ashizuka, Y.; Wasano, C.; Kimura, T.; Moroishi, S.; Urakawa, M.; Sakai, T.; Nishizawa, K.; Hayashi, T.; Matsuura, Y.; Hamada, Y.; Kuba, Y. Antiviral Res., 2020, 180, 104828.
[http://dx.doi.org/10.1016/j.antiviral.2020.104828] [PMID: 32574689]
[5]
Patel, A.; Shah, S.; Ranjan, R.; Shah, S.V.; Patel, K.K. J. Glob. Infect. Dis., 2012, 4(3), 178-181.
[http://dx.doi.org/10.4103/0974-777X.100581] [PMID: 23055650]
[6]
Wang, J.; Jiang, L.; Xu, Y.; He, W.; Zhang, C.; Bi, F.; Tan, Y.; Ning, C. Int. J. Infect. Dis., 2022, 120, 135-141.
[http://dx.doi.org/10.1016/j.ijid.2022.04.045] [PMID: 35477049]
[7]
Li-juan, L.; Kang, S.; Zhi-juan, L.; Dan, L.; Feng, X.; Peng, Y.; Bo-shun, Z.; Jiang, S.; Zhi-jing, X. Vet. Microbiol., 2022, 264, 109303.
[http://dx.doi.org/10.1016/j.vetmic.2021.109303] [PMID: 34923246]
[8]
Adabor, E.S. Heliyon, 2021, 7(11), e08384.
[http://dx.doi.org/10.1016/j.heliyon.2021.e08384] [PMID: 34825090]
[9]
Das, K. J. Med. Chem., 2012, 55(14), 6263-6277.
[http://dx.doi.org/10.1021/jm300455c] [PMID: 22612288]
[10]
Jalily, P.H.; Duncan, M.C.; Fedida, D.; Wang, J.; Tietjen, I. Antiviral Res., 2020, 178, 104780.
[http://dx.doi.org/10.1016/j.antiviral.2020.104780] [PMID: 32229237]
[11]
Chlanda, P. Virology, 2017, 509, 131-132.
[http://dx.doi.org/10.1016/j.virol.2017.06.011] [PMID: 28644977]
[12]
Zhong, Z.J.; Hu, X.T.; Cheng, L.P.; Zhang, X.Y.; Zhang, Q.; Zhang, J. Eur. J. Med. Chem., 2021, 225, 113762.
[http://dx.doi.org/10.1016/j.ejmech.2021.113762] [PMID: 34411893]
[13]
Su, H.C.; Feng, I.J.; Tang, H.J.; Shih, M.F.; Hua, Y.M. J. Infect. Chemother., 2022, 28(2), 158-169.
[http://dx.doi.org/10.1016/j.jiac.2021.11.014] [PMID: 34840038]
[14]
Samson, M.; Pizzorno, A.; Abed, Y.; Boivin, G. Antiviral Res., 2013, 98(2), 174-185.
[http://dx.doi.org/10.1016/j.antiviral.2013.03.014] [PMID: 23523943]
[15]
Kneller, D.W.; Agniswamy, J.; Ghosh, A.K.; Weber, I.T. Biochem. Biophys. Res. Commun., 2019, 519(1), 61-66.
[http://dx.doi.org/10.1016/j.bbrc.2019.08.126] [PMID: 31474336]
[16]
Tompa, D.R.; Immanuel, A.; Srikanth, S.; Kadhirvel, S. Int. J. Biol. Macromol., 2021, 172, 524-541.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.01.076] [PMID: 33454328]
[17]
Herz, C.; Stavnezer, E.; Krug, R.M.; Gurney, T. Jr Cell, 1981, 26(3), 391-400.
[http://dx.doi.org/10.1016/0092-8674(81)90208-7] [PMID: 7326745]
[18]
Gorman, O.T.; Bean, W.J.; Kawaoka, Y.; Webster, R.G. J. Virol., 1990, 64(4), 1487-1497.
[http://dx.doi.org/10.1128/jvi.64.4.1487-1497.1990] [PMID: 2319644]
[19]
Hillaire, M.L.B.; Osterhaus, A.D.M.E.; Rimmelzwaan, G.F. J. Biomed. Biotechnol., 2011, 2011, 1-12.
[http://dx.doi.org/10.1155/2011/939860] [PMID: 22007149]
[20]
Mia, M.; Hasan, M.; Miah, M.M.; Hossain, M.A.S. Vet. Anim. Sci., 2022, 12, 100231.
[21]
Kim, M.H.; Kang, J.O.; Kim, J.Y.; Jung, H.E.; Lee, H.K.; Chang, J. Antiviral Res., 2019, 163, 19-28.
[http://dx.doi.org/10.1016/j.antiviral.2019.01.002] [PMID: 30639307]
[22]
Kao, R.Y.; Yang, D.; Lau, L.S.; Tsui, W.H.W.; Hu, L.; Dai, J.; Chan, M.P.; Chan, C.M.; Wang, P.; Zheng, B.J.; Sun, J.; Huang, J.D.; Madar, J.; Chen, G.; Chen, H.; Guan, Y.; Yuen, K.Y. Nat. Biotechnol., 2010, 28(6), 600-605.
[http://dx.doi.org/10.1038/nbt.1638] [PMID: 20512121]
[23]
Su, C.Y.; Cheng, T.J.R.; Lin, M.I.; Wang, S.Y.; Huang, W.I.; Lin-Chu, S.Y.; Chen, Y.H.; Wu, C.Y.; Lai, M.M.C.; Cheng, W.C.; Wu, Y.T.; Tsai, M.D.; Cheng, Y.S.E.; Wong, C.H. Proc. Natl. Acad. Sci. USA, 2010, 107(45), 19151-19156.
[http://dx.doi.org/10.1073/pnas.1013592107] [PMID: 20974907]
[24]
Gerritz, S.W.; Cianci, C.; Kim, S.; Pearce, B.C.; Deminie, C.; Discotto, L.; McAuliffe, B.; Minassian, B.F.; Shi, S.; Zhu, S.; Zhai, W.; Pendri, A.; Li, G.; Poss, M.A.; Edavettal, S.; McDonnell, P.A.; Lewis, H.A.; Maskos, K.; Mörtl, M.; Kiefersauer, R.; Steinbacher, S.; Baldwin, E.T.; Metzler, W.; Bryson, J.; Healy, M.D.; Philip, T.; Zoeckler, M.; Schartman, R.; Sinz, M.; Leyva-Grado, V.H.; Hoffmann, H.H.; Langley, D.R.; Meanwell, N.A.; Krystal, M. Proc. Natl. Acad. Sci. USA, 2011, 108(37), 15366-15371.
[http://dx.doi.org/10.1073/pnas.1107906108] [PMID: 21896751]
[25]
Cheng, H.; Wan, J.; Lin, M.I.; Liu, Y.; Lu, X.; Liu, J.; Xu, Y.; Chen, J.; Tu, Z.; Cheng, Y.S.E.; Ding, K. J. Med. Chem., 2012, 55(5), 2144-2153.
[http://dx.doi.org/10.1021/jm2013503] [PMID: 22332894]
[26]
Pei, S.; Xia, S.; Yang, F.; Chen, J.; Wang, M.; Sun, W.; Li, Z.; Yuan, K.; Chen, J. RSC Advances, 2020, 10(8), 4446-4454.
[http://dx.doi.org/10.1039/C9RA10828A] [PMID: 35495231]
[27]
Lee, B.; Kang, P.; Lee, K.H.; Cho, J.; Nam, W.; Lee, W.K.; Hur, N.H. Tetrahedron Lett., 2013, 54(11), 1384-1388.
[http://dx.doi.org/10.1016/j.tetlet.2012.12.106]

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