Design, synthesis, antibacterial evaluation and molecular docking studies of some new quinoxaline derivatives targeting dihyropteroate synthase enzyme.
Journal:
Bioorganic chemistry
Published Date:
Dec 5, 2017
Abstract
Development of new antimicrobial agents is a good solution to overcome drug-resistance problems. From this perspective, new quinoxaline derivatives bearing various bioactive heterocyclic moieties (thiadiazoles, oxadiazoles, pyrazoles and thiazoles) were designed and synthesized. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against nine bacterial human pathogenic strains using the disc diffusion assay. In general, most of the synthesized compounds exhibited good antibacterial activities. The thiazolyl 11c displayed significant antibacterial activities against P. aeruginosa (MIC, 12.5 µg/mL vs levofloxacin 12.5 µg/mL). Molecular docking studies indicated that the synthesized compounds could occupy both p-amino benzoic acid (PABA) and pterin binding pockets of the dihydropteroate synthase (DHPS), suggesting that the target compounds could act by the inhibition of bacterial DHPS enzyme. The results provide important information for the future design of more potent antibacterial agents.
Authors
Keywords
Anti-Bacterial Agents
Catalytic Domain
Dihydropteroate Synthase
Drug Design
Gram-Negative Bacteria
Gram-Positive Bacteria
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Levofloxacin
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Structure
Protein Binding
Quinoxalines
Structure-Activity Relationship
Yersinia pestis