Synthesis and Anti-porcine Pseudorabies Virus (PRV) Activity of Novel N-Pyridinium Bipyrazole Dimer Derivatives

doi:10.6023/cjoc202309017

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (5): 1558-1567.DOI: 10.6023/cjoc202309017 Previous Articles Next Articles

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新型含N-吡啶联吡唑类二聚体衍生物的合成及抗猪伪狂犬病毒(PRV)活性评价

侯学会^a, 姚晨^c, 宋锦清^b, 杨菲菲^b, 何张旭^b, 陈晓培^a, 张京玉^b^,^*()

a 河南牧业经济学院理学部郑州 450046
b 河南中医药大学药学院郑州 450046
c 河南农业大学动物医学院郑州 450046

收稿日期:2023-09-18 修回日期:2023-12-15 发布日期:2024-01-30
基金资助:
河南省自然科学基金(202300410264); 河南省科技攻关项目(232102111051); 中国博士后科学基金(2022M721060)

Synthesis and Anti-porcine Pseudorabies Virus (PRV) Activity of Novel N-Pyridinium Bipyrazole Dimer Derivatives

Xuehui Hou^a, Chen Yao^c, Jinqing Song^b, Feifei Yang^b, Zhangxu He^b, Xiaopei Chen^a, Jingyu Zhang^b()

a Faculty of Science, Henan University of Animal Husbandry and Economy, Zhengzhou 450046
b School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou 450046
c College of Veterinary Medicine, Henan Agricultural University Zhengzhou 450046

Received:2023-09-18 Revised:2023-12-15 Published:2024-01-30
Contact: *E-mail: jyzhang2004@126.com
Supported by:
Natural Science Foundation of Henan Province(202300410264); Key Scientific, Technological Project of Henan Province(232102111051); China Postdoctoral Science Foundation(2022M721060)

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Abstract

The porcine pseudorabies virus (PRV) leading to severe neurological and respiratory damage can infect a wide range of vertebrates and humans, which raises concerns regarding the potential cross-species transmission of PRV. However, there is currently a lack of specific antiviral treatments available for PRV. 25 dimer derivatives containing N-pyridine bipyrazole moiety were designed and synthesized based on the principles of molecular splicing and electron isoarrangement. The inhibitory effect of the target compounds on PRV virus was assessed. Preliminary bioassay revealed that most of the compounds exhibited potent anti-PRV activity at a concentration of 10 μmol/L while demonstrating no or minimal toxicity towards a type of porcine kidney cell (PK-15). These novel N-pyridinium bipyrazole dimer derivatives could be regarded as anti-PRV agents for further optimization and development.

Key words: N-pyridinium bipyrazole, dimer derivative, anti-porcine pseudorabies virus (PRV) activity

Cite this article

Xuehui Hou, Chen Yao, Jinqing Song, Feifei Yang, Zhangxu He, Xiaopei Chen, Jingyu Zhang. Synthesis and Anti-porcine Pseudorabies Virus (PRV) Activity of Novel N-Pyridinium Bipyrazole Dimer Derivatives[J]. Chinese Journal of Organic Chemistry, 2024, 44(5): 1558-1567.

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Fig. & Tab. 6

Figure 1. Reported STING agonists (SR717, P-1 and diABZ11) and anti-herpesvirus drugs (J-1)

Figure 2. Design strategy of the target compounds

Scheme 1. Synthetic route of target compounds 6~30 Reagents and conditions: (a) diethyl oxalate, NaOCH3, EtOH, 0 ℃; (b) NH2NH2?H2O, EtOH, 85 ℃; (c) 1,4-dibromobutane, KOH, DMSO, MW; (d) NaOH, CH3OH, 90 ℃; (e) substituted aniline, EDCI, HOBT, DIPEA, 80 ℃

Figure 3. (A) Crystal structure, (B) cell stacking diagram and (C) intermolecular hydrogen bond force of compound 14

Figure 4. Effect of target compounds 6~30 on the proliferation of PRV-GFP detected by flow cytometry

Figure 5. Inhibition rates of some compounds on PK-15 cells

References 33

[1]	Ketusing, N.; Reeves, A.; Portacci, K.; Yano, T.; Olea-Popelka, F.; Keefe, T.; Salman, M. Transboundary Emerging Dis. 2014, 61, 169.
[2]	Zhou, M.; Abid, M.; Cao, S.; Zhu, S. Viruses 2022, 14, 1753.
[3]	Li, X. D.; Fu, S. H.; Chen, L. Y.; Li, F.; Deng, J. H.; Lu, X. C.; Wang, H. Y.; Tian, K. G. Biomed. Environ. Sci. 2020, 33, 444.
[4]	Liu, Q.; Wang, X.; Xie, C.; Ding, S.; Yang, H.; Guo, S.; Li, J.; Qin, L.; Ban, F.; Wang, D.; Wang, C.; Feng, L.; Ma, H.; Wu, B.; Zhang, L.; Dong, C.; Xing, L.; Zhang, J.; Chen, H.; Yan, R.; Wang, X.; Li, W. Clin. Infect. Dis. 2021, 73, e3690.
[5]	Wang, D.; Tao, X.; Fei, M.; Chen, J.; Guo, W.; Li, P.; Wang, J. J. Neurovirol. 2020, 26, 442. doi: 10.1007/s13365-019-00822-2 pmid: 31898060
[6]	Pomeranz, L. E.; Reynolds, A. E.; Hengartner, C. J. Microbiol. Mol. Biol. Rev. 2005, 69, 462.
[7]	Yang, L.; Wang, M.; Cheng, A.; Yang, Q.; Wu, Y.; Jia, R.; Liu, M.; Zhu, D.; Chen, S.; Zhang, S.; Zhao, X.; Huang, J.; Wang, Y.; Xu, Z.; Chen, Z.; Zhu, L.; Luo, Q.; Liu, Y.; Yu, Y.; Zhang, L.; Tian, B.; Pan L; Rehman, M. U.; Chen, X. Front. Immunol. 2019, 10, 2196.
[8]	Xie, J.; Li, X.; Yang S; Yan, Z.; Chen, L.; Yang, Y.; Li, D.; Zhang, X.; Feng, R. Front. Microbiol. 2022, 13, 932842.
[9]	Kong, Z.; Yin, H.; Wang, F.; Liu, Z.; Luan, X.; Sun, L.; Liu, W.; Shang, Y. PLoS Pathog. 2022, 18, e1010544.
[10]	Lu, X.; Wang, X.; Cheng, H.; Wang, X.; Liu, C.; Tan, X. Ann. Med. 2023, 55, 2210845.
[11]	Xu, L.; Liu, M.; Chen, H.; Zhang, L.; Xu, Q.; Zhan, Z.; Xu, Z.; Liu, S.; Wu, S.; Zhang, X.; Qin, Q.; Wei, J. Fish Shellfish Immunol. 2023, 140, 108990.
[12]	Du, H.; Kou, M.; Deng, W.; Zhou, X.; Zhang, X.; Huang, Z.; Ren, B.; Cai, X.; Xu, S.; Chen, Y.; Chen, L.; Chen, C.; Bao, H.; Chen, Q.; Li, D. Biomed. Pharmacother. 2023, 165, 115188.
[13]	Ramanjulu, J. M.; Pesiridis, G. S.; Yang, J.; Concha, N.; Singhaus, R.; Zhang, S. Y.; Tran, J. L.; Moore, P.; Lehmann, S.; Eberl, H. C.; Muelbaier, M.; Schneck, J. L.; Clemens, J.; Adam, M.; Mehlmann, J.; Romano, J.; Morales, A.; Kang, J.; Leister, L.; Graybill, T. L.; Charnley, A. K.; Ye, G.; Nevins, N.; Behnia, K.; Wolf, A. I.; Kasparcova, V.; Nurse, K.; Wang, L.; Puhl, A. C.; Li, Y.; Klein, M.; Hopson, C. B.; Guss, J.; Bantscheff, M.; Bergamini, G.; Reilly, M. A.; Lian, Y.; Duffy, K. J.; Adams, J.; Foley, K. P.; Gough, P. J.; Marquis, R. W.; Smothers, J.; Hoos, A.; Bertin, J. Nature 2018, 564, 439.
[14]	Liu, Y.; Lu, X.; Qin, N.; Qiao, Y.; Xing, S.; Liu, W.; Feng, F.; Liu, Z.; Sun, H. Eur. J. Med. Chem. 2021, 211, 113113.
[15]	Berthelot, J. M.; Lioté, F.; Maugars, Y.; Sibilia, J. Front. Immunol. 2020, 11, 607069.
[16]	Hou, S.; Lan, X. J.; Li, W.; Yan, X. L.; Chang, J. J.; Yang, X. H.; Sun, W.; Xiao, J. H.; Li, S. Bioorg. Chem. 2020, 95, 103556.
[17]	Song, X.; Peng, Y.; Wang, X.; Chen, Q.; Lan, X.; Shi, F. Clin. Transl. Oncol. 2023, 25, 1545.
[18]	Chin, E. N.; Yu, C.; Vartabedian, V. F.; Jia, Y.; Kumar, M.; Gamo, A. M.; Vernier, W.; Ali, S. H.; Kissai, M.; Lazar, D. C.; Nguyen, N.; Pereira, L. E.; Benish, B.; Woods, A.K.; Joseph, S. B.; Chu, A.; Johnson, K. A.; Sander, P. N.; Martínez-Peña, F.; Hampton, E. N.; Young, T. S.; Wolan, D. W.; Chatterjee, A. K.; Schultz, P. G.; Petrassi, H. M.; Teijaro, J. R.; Lairson, L. L. Science 2020, 369, 993.
[19]	Sali, T. M.; Pryke, K. M.; Abraham, J.; Liu, A.; Archer, I.; Broeckel, R.; Staverosky, J. A.; Smith, J. L.; Al-Shammari, A.; Amsler, L.; Sheridan, K.; Nilsen, A.; Streblow, D. N.; DeFilippis, V. R. PLoS Pathog. 2015, 11, e1005324.
[20]	Luo, M.; Groaz, E.; Snoeck, R.; Andrei, G.; Herdewijn, P. ACS Med. Chem. Lett. 2020, 11, 1410.
[21]	Suita, K.; Fujita, T.; Cai, W.; Hidaka, Y.; Jin, H.; Prajapati, R.; Umemura, M.; Yokoyama, U.; Sato, M.; Knollmann, B. C.; Okumura, S.; Ishikawa, Y. Pflugers Arch. 2018, 470, 923.
[22]	Pertusati, F.; Serafini, S.; Albadry, N.; Snoeck, R.; Andrei, G. Antiviral Res. 2017, 143, 262.
[23]	Hew, K.; Dahlroth, S. L.; Veerappan, S.; Pan, L. X.; Cornvik, T.; Nordlund, P. PLoS One. 2015, 10, e0143947.
[24]	Johns, B. A.; Gudmundsson, K. S.; Turner, E. M.; Allen, S. H.; Samano, V. A.; Ray, J. A.; Freeman, G. A.; Boyd, F. L.; Sexton, C. J.; Selleseth, D. W.; Creech, K. L.; Moniri, K. R. Bioorg. Med. Chem. 2005, 13, 2397.
[25]	Safdar, M. H.; Hasan, H.; Afzal, S.; Hussain, Z. Mini. Rev. Med. Chem. 2018, 18, 1047.
[26]	Sribalan, R.; Banuppriya, G.; Kirubavathi, M.; Jayachitra, A.; Padmini, V. Bioorg. Med. Chem. Lett. 2016, 26, 5624.
[27]	Bauer, V. J.; Dalalian, H. P.; Fanshawe, W. J.; Safir, S. R. J. Med. Chem. 1968, 11, 981. pmid: 5697110
[28]	Madhu, P.; Sivakumar, P. J. Photochem. 2019, 371, 341.
[29]	Nithyabalaji, R.; Krishnan, H.; Sribalan, R. J. Mol. Struct. 2019, 1186, 1. doi: 10.1016/j.molstruc.2019.02.095
[30]	Wiatrak, B.; Kubis-Kubiak, A.; Piwowar, A.; Barg, E. Cells 2020, 9, 958.
[31]	Massai, D.; Isu, G.; Madeddu, D.; Cerino, G.; Falco, A.; Frati, C.; Gallo, D.; Deriu, M. A.; Falvo, D'Urso Labate G. ; Quaini, F.; Audenino, A.; Morbiducci, U. PLoS One. 2016, 11, e0154610.
[32]	Das, R.; Roosloot, R.; van Pel, M.; Schepers, K.; Driessen, M.; Fibbe, W. E.; de Bruijn, J. D.; Roelofs, H. J. Transl. Med. 2019, 17, 241.
[33]	Huang, J.; Qi, Y.; Wang, A.; Huang, C.; Liu, X.; Yang, X.; Li, L.; Zhou, R. Virol. J. 2020, 17, 18. doi: 10.1186/s12985-020-1288-4 pmid: 32014007

新型含N-吡啶联吡唑类二聚体衍生物的合成及抗猪伪狂犬病毒(PRV)活性评价

Synthesis and Anti-porcine Pseudorabies Virus (PRV) Activity of Novel N-Pyridinium Bipyrazole Dimer Derivatives

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