Synthesis and molecular docking study of α-aminophosphonates as potential multi-targeting antibacterial agents

Rana R Neiber; Nadia A Samak; Jianmin Xing; Elshaymaa I Elmongy; Ahmed A Galhoum; Ibrahim El-Tantawy El Sayed; Eric Guibal; Jiayu Xin; Xingmei Lu

doi:10.1016/j.jhazmat.2023.133203

Synthesis and molecular docking study of α-aminophosphonates as potential multi-targeting antibacterial agents

J Hazard Mater. 2024 Mar 5:465:133203. doi: 10.1016/j.jhazmat.2023.133203. Epub 2023 Dec 12.

Authors

Rana R Neiber¹, Nadia A Samak², Jianmin Xing³, Elshaymaa I Elmongy⁴, Ahmed A Galhoum⁵, Ibrahim El-Tantawy El Sayed⁶, Eric Guibal⁷, Jiayu Xin⁸, Xingmei Lu⁹

Affiliations

¹ Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China; College of Chemical Engineering, University of Chinese Academy of Sciences, 19 A Yuquan Road, 100049 Beijing, China; School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, 100049 Beijing, China.
² College of Chemical Engineering, University of Chinese Academy of Sciences, 19 A Yuquan Road, 100049 Beijing, China; CAS Key Laboratory of Green Process and Engineering & State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; Aquatic microbiology department, Faculty of Chemistry, University of Duisburg-Essen, 45141 Essen, Germany. Electronic address: nadia@ipe.ac.cn.
³ College of Chemical Engineering, University of Chinese Academy of Sciences, 19 A Yuquan Road, 100049 Beijing, China; CAS Key Laboratory of Green Process and Engineering & State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. BOX 84428, Riyadh 11671, Saudi Arabia.
⁵ Nuclear Materials Authority, P.O. Box 530, El-Maadi, Cairo, Egypt. Electronic address: galhoum_nma@yahoo.com.
⁶ Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, Egypt. Electronic address: ibrahimtantawy@yahoo.co.uk.
⁷ Institut Mines Telecom-Mines Alès, C2MA, 6 avenue de Clavières, F-30319 Alès cedex, France.
⁸ Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China; School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, 100049 Beijing, China; Innovation Academy for Green Manufacture, Chinese Academy of Sciences, Beijing 100190, China.
⁹ Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 100190 Beijing, China; School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, 100049 Beijing, China; Innovation Academy for Green Manufacture, Chinese Academy of Sciences, Beijing 100190, China; Department of Chemistry, University of Chinese Academy of Sciences, 100049 Beijing, China. Electronic address: xmlu@ipe.ac.cn.

PMID: 38103294
DOI: 10.1016/j.jhazmat.2023.133203

Abstract

Antibacterial compounds that reduce extracellular polymeric substances (EPS) are needed to avoid bacterial biofilms in water pipelines. Herein, green one-pot synthesis of α-aminophosphonates (α-Amp_s) [A-G] was achieved by using ionic liquid (IL) as a Lewis acid catalyst. The synthesized α-Amp analogues were tested against different bacteria such as Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The representative [B] analogue showed an efficient antibacterial effect with MIC values of 3.13 μg/mL for E. coli, P. aeruginosa, and 6.25 μg/mL for B. subtilis. Additionally, a strong ability to eliminate the mature bacterial biofilm, with super-MIC values of 12.5 μg/mL for E. coli, P. aeruginosa, and 25 μg/mL for B. subtilis. Moreover, bacterial cell disruption by ROS formation was also tested, and the compound [B] revealed the highest ROS level compared to other compounds and the control, and efficiently destroyed the extracellular polymeric substances (EPS). The docking study confirmed strong interactions between [B] analogue and protein structures with a binding affinity of -6.65 kCal/mol for the lyase protein of gram-positive bacteria and -6.46 kCal/mol for DNA gyrase of gram-negative bacteria. The results showed that α-Amp_s moiety is a promising candidate for developing novel antibacterial and anti-biofilm agents for clean water supply.

Keywords: Aminophosphonates; Anti-bacterial; Anti-biofilm; Bacteria; Docking study.

MeSH terms

Anti-Bacterial Agents* / chemistry
Bacteria
Biofilms
Escherichia coli*
Microbial Sensitivity Tests
Molecular Docking Simulation
Reactive Oxygen Species

Substances

Anti-Bacterial Agents
Reactive Oxygen Species