Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking

Molecules. 2017 Aug 16;22(8):1352. doi: 10.3390/molecules22081352.

Abstract

Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC50 = 0.081 ± 0.003 µM), 6a (IC50 = 0.0022 ± 0.0002 µM), 9e (IC50 = 0.0250 ± 0.0007 µM) and 12d (IC50 = 0.0266 ± 0.0021 µM) were found to be the lead compounds compared to standard (thiourea, IC50 = 17.814 ± 0.096 µM). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e, 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a, 12b, 12d, 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C.

Keywords: drug derivatives; drug discovery; jack bean urease inhibition; kinetic mechanism; molecular docking; sulfonamides.

MeSH terms

  • Amantadine / analogs & derivatives
  • Amantadine / chemical synthesis
  • Amantadine / chemistry
  • Ciprofloxacin / analogs & derivatives
  • Ciprofloxacin / chemical synthesis
  • Ciprofloxacin / chemistry
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Fabaceae / chemistry
  • Fabaceae / enzymology
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry*
  • Inhibitory Concentration 50
  • Kinetics
  • Molecular Docking Simulation
  • Structure-Activity Relationship
  • Sulfadiazine / analogs & derivatives
  • Sulfadiazine / chemical synthesis
  • Sulfadiazine / chemistry
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Urease / antagonists & inhibitors*
  • Urease / chemistry

Substances

  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Sulfonamides
  • Sulfadiazine
  • Ciprofloxacin
  • Amantadine
  • Urease