2. Academic Validation
  3. Design, regioselective, time gated synthesis of novel benzo[d]imidazole analogues as potential quorum sensing inhibitors targeting LasR in Pseudomonas aeruginosa

Design, regioselective, time gated synthesis of novel benzo[d]imidazole analogues as potential quorum sensing inhibitors targeting LasR in Pseudomonas aeruginosa

  • Bioorg Chem. 2026 Apr:171:109561. doi: 10.1016/j.bioorg.2026.109561.
Esraa Z Mohammed 1,  Heba S Rateb 2,  Amira A Helwa 3,  Nourhan G Naga 4,  Mona E M Mabrouk 5,  Ahmed B M Mehany 6,  Hatem A Abdel Aziz 7,  Nehad M El-Dydamony 8
Affiliations

Affiliations

  • 1 Pharmaceutical Chemistry Department, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt. Electronic address: dr.esraazakaria@o6u.edu.eg.
  • 2 Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, P. O. Box: 77, 6th of October City, Egypt.
  • 3 Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, P. O. Box: 77, 6th of October City, Egypt.
  • 4 Department of Botany and Microbiology, Faculty of Science, Alexandria University, Alexandria, Egypt.
  • 5 Department of Botany and Microbiology, Faculty of Science, Damanhour University, Damanhour, Egypt.
  • 6 Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt.
  • 7 Applied Organic Chemistry Department, National Research Centre, Dokki, Giza, P.O. Box 12622, Egypt. Electronic address: ha.abdel-azizz@nrc.sci.eg.
  • 8 Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, P. O. Box: 77, 6th of October City, Egypt. Electronic address: nehad.eldydamony@must.edu.eg.
PMID: 41616526 DOI: 10.1016/j.bioorg.2026.109561
Abstract

The rapid emergence of antibiotic-resistant pathogens highlights the crucial need for alternate anti-infective strategies. Quorum sensing inhibition (QSI) offers compelling approaches to attenuate Bacterial virulence while limiting the resistance. In this study, fourteen Benzo[d]imidazole derivatives were synthesized and proposed as potential LasR antagonists exhibiting quorum-sensing inhibitory activity. Among these, compounds 7f, 7 h, 11b, 11c, and 11f demonstrated a marked ability to suppress biofilm formation in P. aeruginosa by (83%, 87%, 84%, 87%, 86%), pyocyanin production (76%, 84%, 86%, 82%, 81%), and motility activity; swimming (90%, 86%, 91%, 88%, 90%), twitching (90%, 94%, 93%, 86%, 92%), respectively. Additionally, compounds 7f and 11c effectively inhibited LasR, with IC50 values equal to 0.74 ± 0.005, 0.79 ± 0.001 μM, respectively. Moreover, a 200-ns molecular dynamics simulation (MDS) of the 7f analogue indicated its potential to disrupt the dimeric structure of the LasR protein, thereby confirming its inhibitory activity toward LasR. Collectively, these results establish benzo[d]imidazole scaffolds as promising leads for the development of next-generation quorum sensing modulators aimed at disarming Bacterial pathogenicity and countering antimicrobial resistance.

Keywords

Benzo[d]imidazoles; LasR; MD simulation; P. aeruginosa; QSI.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z