Synthesis of Disulfide-Bridged N-Phenyl-N'-(alkyl/aryl/heteroaryl)urea Derivatives and Evaluation of Their Antimicrobial Activities

Chem Biodivers. 2019 Dec;16(12):e1900461. doi: 10.1002/cbdv.201900461. Epub 2019 Nov 11.


The discovery of new antimicrobial agents is extremely needed to overcome multidrug-resistant bacterial and tuberculosis infections. In the present study, eight novel substituted urea derivatives (10a-10h) containing disulfide bond were designed, synthesized and screened for their in vitro antimicrobial activities on standard strains of Gram-positive and Gram-negative bacteria as well as on Mycobacterium tuberculosis. According to the obtained results, antibacterial effects of the compounds were found to be considerably better than their antimycobacterial activities along with their weak cytotoxic effects. Molecular docking studies were performed to gain insights into the antibacterial activity mechanism of the synthesized compounds. The interactions and the orientation of compound 10a (1,1'-((disulfanediylbis(methylene))bis(2,1-phenylene))bis(3-phenylurea)) were found to be highly similar to the original ligand within the binding pocket E. faecalis β-ketoacyl acyl carrier protein synthase III (FabH). Finally, a theoretical study was established to predict the physicochemical properties of the compounds.

Keywords: antibacterial activity; dimerization; drug design; synthesis; urea.

MeSH terms

  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / chemistry
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / metabolism
  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / pharmacology
  • Binding Sites
  • Cell Survival / drug effects
  • Disulfides / chemistry*
  • Enterococcus faecalis / enzymology
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • RAW 264.7 Cells
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / pharmacology


  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Disulfides
  • Urea
  • 3-ketoacyl-acyl carrier protein synthase III
  • 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase