Citation: Wenzhang Chen, Xingyue Wang, Pengyi Yan, Weidong Pan, Xuemin Jia, Yi Chen, Lina Liang, Jing Huang, Lirong Liu, Stéphane P. Vincent, Lei Tang. Functionalized copillar[3+2]arene: A programmable scaffold for dual-targeting biofilm inhibitors against Pseudomonas aeruginosa[J]. Chinese Chemical Letters, ;2026, 37(12): 112942. doi: 10.1016/j.cclet.2026.112942 shu

Functionalized copillar[3+2]arene: A programmable scaffold for dual-targeting biofilm inhibitors against Pseudomonas aeruginosa

Wenzhang Chen ^{a, 1} ,
Xingyue Wang ^{a, 1} ,
Pengyi Yan ^{a, 1} ,
Weidong Pan ^a ,
Xuemin Jia ^a ,
Yi Chen ^a ,
Lina Liang ^b ,
Jing Huang ^{a, *,} ,
Lirong Liu ^{a, *,} ,
Stéphane P. Vincent ^{c, *,} ,
Lei Tang ^{a, *,}

a.
The Affiliated Hospital of Guizhou Medical University, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang 561113, China
b.
Department of Chemistry, Bengbu Medical University, Bengbu 233030, China
c.
Department of Chemistry, University of Namur, Rue de Bruxelles 61, Namur B-5000, Belgium

huangjgy@sohu.com

lirongliu@gmc.edu.cn

stephane.vincent@unamur.be

tlei1974@163.com

Received Date: 28 January 2026
Revised Date: 12 May 2026
Accepted Date: 13 May 2026
Available Online: 14 May 2026

Figures(7)

Herein, we report an efficient fragment co-cyclization strategy for the synthesis of an orthogonally functionalized copillar[3 + 2]arene bearing propargyl and bromoethyl groups, achieving a yield of up to 50%. Its programmable architecture was unambiguously confirmed by single-crystal X-ray diffraction. This versatile scaffold enabled the precise construction of the water-soluble glycopeptide mimic GM10 via sequential orthogonal click reactions. GM10, featuring rationally integrated lectin-targeting and cationic modules, exhibits a dual inhibitory mechanism: It competitively binds to the Pseudomonas aeruginosa (P. aeruginosa) lectin LecB to block lectin-mediated adhesion, while simultaneously sequestering the key quorum-sensing (QS) signal molecule 3-oxo-C12-HSL through host–guest complexation, thereby suppressing QS and attenuating virulence factor expression. This mimic demonstrates potent, non-bactericidal anti-biofilm activity in vitro and accelerates wound healing in a murine infection model. Our work not only presents a novel synthetic route to functionalized pillar[5]arenes but also underscores the potential of programmable copillar[3 + 2]arene scaffolds for developing next-generation anti-virulence agents against biofilm-associated resistance.
- Functionalized pillararenes,
- Synthesis,
- Glycopeptide,
- Anti-biofilm,
- LecB,
- QS quenching
1. [1]
  M. Masi, M. Réfregiers, K.M. Pos, et al., Nat. Microbiol. 2 (2017) 17001. doi: 10.1038/nmicrobiol.2017.1
2. [2]
  E. Rossi, R. La Rosa, J.A. Bartell, et al., Nat. Rev. Microbiol. 19 (2021) 331–342. doi: 10.1038/s41579-020-00477-5
3. [3]
  D. Lebeaux, J.M. Ghigo, C. Beloin, Microbiol. Mol. Biol. Rev. 78 (2014) 510–543. doi: 10.1128/MMBR.00013-14
4. [4]
  R. Loris, D. Tielker, K.E. Jaeger, et al., J. Mol. Biol. 331 (2003) 861–870. doi: 10.1016/S0022-2836(03)00754-X
5. [5]
  C. Chemani, A. Imberty, S. de Bentzmann, et al., Infect. Immun. 77 (2009) 2065–2075. doi: 10.1128/IAI.01204-08
6. [6]
  D. Passos da Silva, M.L. Matwichuk, D.O. Townsend, et al., Nat. Commun. 10 (2019) 2183. doi: 10.1038/s41467-019-10201-4
7. [7]
  D. Tielker, S. Hacker, R. Loris, et al., Microbiology 151 (2005) 1313–1323. doi: 10.1099/mic.0.27701-0
8. [8]
  K. Winzer, C. Falconer, N.C. Garber, et al., J. Bacteriol. 182 (2000) 6401–6411. doi: 10.1128/JB.182.22.6401-6411.2000
9. [9]
  T. Krell, M.A. Matilla, Trends Microbiol. 32 (2024) 216–218. doi: 10.1016/j.tim.2023.11.005
10. [10]
  S.P. Diggle, R.E. Stacey, C. Dodd, et al., Environ. Microbiol. 8 (2006) 1095–1104. doi: 10.1111/j.1462-2920.2006.001001.x
11. [11]
  T. De Kievit, Environ. Microbiol. 11 (2009) 279–288. doi: 10.1111/j.1462-2920.2008.01792.x
12. [12]
  M. Whiteley, S.P. Diggle, E.P. Greenberg, Nature 551 (2017) 313–320. doi: 10.1038/nature24624
13. [13]
  A. Maiga, M. Ampomah-Wireko, H. Li, et al., Eur. J. Med. Chem. 281 (2025) 117008. doi: 10.1016/j.ejmech.2024.117008
14. [14]
  S. Leusmann, P. Ménová, E. Shanin, et al., Chem. Soc. Rev. 52 (2023) 3663–3740. doi: 10.1039/d2cs00954d
15. [15]
  D. Tang, Y. Lin, H. Yao, et al., Appl. Microbiol. Biotechnol. 108 (2024) 418. doi: 10.1007/s00253-024-13247-7
16. [16]
  J.E. Paczkowski, A.R. McCready, J.P. Cong, et al., ACS Chem. Biol. 14 (2019) 378–389. doi: 10.1021/acschembio.8b00971
17. [17]
  J. Fong, M. Yuan, T.H. Jakobsen, et al., J. Med. Chem. 60 (2017) 215–227. doi: 10.1021/acs.jmedchem.6b01025
18. [18]
  H.Z. Long, W. Tang, M.Y. Huang, et al., J. Med. Chem. 68 (2025) 14756–14781. doi: 10.1021/acs.jmedchem.5c00909
19. [19]
  C.T. O’Loughlin, L.C. Miller, A. Siryaporn, et al., Proc. Natl. Acad. Sci. U. S. A. 110 (2013) 17981–17986. doi: 10.1073/pnas.1316981110
20. [20]
  Y. Wang, L. Pan, L. Li, et al., Eur. J. Med. Chem. 238 (2022) 114457. doi: 10.1016/j.ejmech.2022.114457
21. [21]
  D. Wu, B. Wu, J. Li, et al., J. Mol. Struct. 1340 (2025) 142533. doi: 10.1016/j.molstruc.2025.142533
22. [22]
  M.A. Rather, D. Saha, S. Bhuyan, et al., Microbiol. Res. 264 (2022) 127173. doi: 10.1016/j.micres.2022.127173
23. [23]
  G. Antonini, M. Fares, D. Hauck, et al., J. Med. Chem. 68 (2025) 9681–9693. doi: 10.1021/acs.jmedchem.5c00405
24. [24]
  S.R. Borgert, S. Henke, F. Witzgall, et al., Nat. Commun. 13 (2022) 7402. doi: 10.1038/s41467-022-35030-w
25. [25]
  T.X. Zhang, S. Peng, S.X. Zhang, et al., Chem. Eng. J. 518 (2025) 164500. doi: 10.1016/j.cej.2025.164500
26. [26]
  N. Song, T. Kakuta, T. Yamagishi, et al., Chem 4 (2018) 2029–2053. doi: 10.1016/j.chempr.2018.05.015
27. [27]
  T. Ogoshi, T. Yamagishi, Y. Nakamoto, Chem. Rev. 116 (2016) 7937–8002. doi: 10.1021/acs.chemrev.5b00765
28. [28]
  Q. Li, H. Zhu, F. Huang, Trends Chem. 2 (2020) 850–864. doi: 10.1016/j.trechm.2020.07.004
29. [29]
  Z. Shen, S. Chao, L. Wu, et al., Chem. Soc. Rev. 54 (2025) 8345–8405. doi: 10.1039/d4cs00458b
30. [30]
  W. Yang, W. Zhang, J. Chen, et al., Chin. Chem. Lett. 35 (2024) 108740. doi: 10.1016/j.cclet.2023.108740
31. [31]
  S. Guo, H. Xu, Z. Cheng, et al., Chin. Chem. Lett. 36 (2025) 111022. doi: 10.1016/j.cclet.2025.111022
32. [32]
  M. Yan, Y. Wang, J. Chen, et al., Chem. Soc. Rev. 52 (2023) 6075–6119. doi: 10.1039/d2cs00856d
33. [33]
  J. Chen, S. Wu, Y. Wang, et al., Chin. Chem. Lett. 36 (2025) 110102. doi: 10.1016/j.cclet.2024.110102
34. [34]
  C. Buranello, M. Da Pian, T. Lorenzetto, et al., ACS Catal. 14 (2024) 15850–15857. doi: 10.1021/acscatal.4c04836
35. [35]
  M. Yan, G. Yu, M. Wang, et al., Cell Rep. Phys. Sci. 5 (2024) 102307. doi: 10.1016/j.xcrp.2024.102307
36. [36]
  Q. Li, K. Hu, S. Xu, et al., ACS Macro Lett. 14 (2025) 120–128. doi: 10.1021/acsmacrolett.4c00826
37. [37]
  M. Yan, C. Liu, R. Tang, et al., Adv. Sci. 13 (2026) e12924. doi: 10.1002/advs.202512924
38. [38]
  S. Jothi Nayaki, A. Roja, R. Ravindhiran, et al., ACS Infect. Dis. 10 (2024) 1080–1096. doi: 10.1021/acsinfecdis.3c00697
39. [39]
  Y. Zhang, P. Zhang, Y. Lv, et al., ACS Appl. Bio Mater. 7 (2024) 7730–7739. doi: 10.1021/acsabm.4c01305
40. [40]
  Y. Jin, Y. Liu, J. Zhu, et al., Org. Biomol. Chem. 22 (2024) 4202–4211. doi: 10.1039/d4ob00396a
41. [41]
  D. Kaizerman-Kane, M. Hadar, R. Joseph, et al., ACS Infect. Dis. 7 (2021) 579–585. doi: 10.1021/acsinfecdis.0c00662
42. [42]
  T. Mohy El Dine, R. Jimmidi, A. Diaconu, et al., J. Med. Chem. 64 (2021) 14728–14744. doi: 10.1021/acs.jmedchem.1c01241
43. [43]
  W. Chen, T.Mohy El Dine, S.P. Vincent, Chem. Commun. 57 (2021) 492–495. doi: 10.1039/d0cc07684h
44. [44]
  I.M. Andrei, W. Chen, M. Baaden, et al., J. Am. Chem. Soc. 145 (2023) 21904–21914. doi: 10.1021/jacs.3c06335
45. [45]
  W. Mao, S. Zhan, B. Zhu, et al., J. Org. Chem. 83 (2018) 4147–4152. doi: 10.1021/acs.joc.8b00073
46. [46]
  H. Yang, L. Jin, D. Zhao, et al., J. Agric. Food Chem. 69 (2021) 4276–4283. doi: 10.1021/acs.jafc.1c01032
47. [47]
  A.M. Boukerb, A. Rousset, N. Galanos, et al., J. Med. Chem. 57 (2014) 10275–10289. doi: 10.1021/jm500038p
48. [48]
  Z. Liu, F. Demontrond, A. Imberty, et al., Chin. Chem. Lett. 34 (2023) 107872. doi: 10.1016/j.cclet.2022.107872
49. [49]
  K. Buffet, I. Nierengarten, N. Galanos, et al., Chem. Eur. J. 22 (2016) 2955–2963. doi: 10.1002/chem.201504921
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