Fungal biofilm inhibition by piperazine-sulphonamide linked Schiff bases: Design, synthesis, and biological evaluation

Arch Pharm (Weinheim). 2018 Apr;351(3-4):e1700354. doi: 10.1002/ardp.201700354. Epub 2018 Mar 15.

Abstract

We report the synthesis of some new piperazine-sulphonamide linked Schiff bases as fungal biofilm inhibitors with antibacterial and antifungal potential. The biofilm inhibition result of Candida albicans proposed that the compounds 6b (IC50 = 32.1 μM) and 6j (IC50 = 31.4 μM) showed higher inhibitory activity than the standard fluconazole (IC50 = 40 μM). Compound 6d (MIC = 26.1 μg/mL) with a chloro group at the para position was found to be the most active antibacterial agent of the series against Bacillus subtilis when compared with the standard ciprofloxacin (MIC = 50 μg/mL). Compound 6j (MIC = 39.6 μg/mL) with an OH group at the ortho position showed more potent antifungal activity as compared to that of the standard fluconazole (IC50 = 50 μM) against C. albicans. Thus, the synthesized compounds 6a-k were found to be potent biofilm inhibitors as well as active antibacterial and antifungal agents. The molecular docking study of the synthesized compounds against the secreted aspartyl protease (SAP5) enzyme of C. albicans exhibited good binding properties. The in silico ADME properties of the synthesized compounds were also analyzed and showed their potential to be developed as potential oral drug candidates.

Keywords: Schiff bases; antibacterial; fungal biofilm inhibition; piperazine; sulphonamide.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Bacillus subtilis / drug effects
  • Biofilms / drug effects*
  • Candida albicans / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Piperazine
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Pseudomonas aeruginosa / drug effects
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Structure-Activity Relationship
  • Sulfanilamide
  • Sulfanilamides / chemistry
  • Sulfanilamides / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Piperazines
  • Schiff Bases
  • Sulfanilamides
  • Piperazine
  • Sulfanilamide