SIOC English
有机化学
高级检索

有机化学 >

2024 , Vol. 44 >Issue 5: 1558 - 1567

DOI: https://doi.org/10.6023/cjoc202309017

研究论文

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 ,
  • 姚晨 ,
  • 宋锦清 ,
  • 杨菲菲 ,
  • 何张旭 ,
  • 陈晓培 ,
  • 张京玉
展开
  • 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

  网络出版日期: 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)

收起

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

  • Xuehui Hou ,
  • Chen Yao ,
  • Jinqing Song ,
  • Feifei Yang ,
  • Zhangxu He ,
  • Xiaopei Chen ,
  • Jingyu Zhang
Expand
  • 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
*E-mail:

Received date: 2023-09-18

  Revised date: 2023-12-15

  Online published: 2024-01-30

Supported by

Natural Science Foundation of Henan Province(202300410264); Key Scientific, Technological Project of Henan Province(232102111051); China Postdoctoral Science Foundation(2022M721060)

Fold

摘要

猪伪狂犬病毒(PRV)不仅感染多种脊椎动物, 还可直接感染人类, 导致神经和呼吸系统严重受损, 引起了人们对PRV跨物种传播的担忧, 然而, 针对PRV的特异性抗病毒药物很少. 运用分子拼接和电子等排的原理, 设计合成了25个含N-吡啶联吡唑类二聚体衍生物, 并测试了目标化合物对PRV病毒的抑制效果. 初步生物活性测试数据显示, 大多数化合物在10 μmol/L浓度下表现出较强的抗PRV病毒活性, 且对猪源肾上皮细胞(PK-15)具有无毒性或者低毒性. 此类新型含N-吡啶联吡唑类二聚体衍生物可作为潜在抗PRV病毒的先导化合物进一步优化和开发.

关键词： N-吡啶联吡唑; 二聚体; 抗猪伪狂犬病毒(PRV)活性

本文引用格式

侯学会 , 姚晨 , 宋锦清 , 杨菲菲 , 何张旭 , 陈晓培 , 张京玉 . 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[J]. 有机化学, 2024 , 44(5) : 1558 -1567 . DOI: 10.6023/cjoc202309017

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

参考文献

[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.
[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-Pe?a, 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.
[28]
Madhu, P.; Sivakumar, P. J. Photochem. 2019, 371, 341.
[29]
Nithyabalaji, R.; Krishnan, H.; Sribalan, R. J. Mol. Struct. 2019, 1186, 1.
[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.
Options
文章导航

/

〈 〉