Design, synthesis, antibacterial evaluation and molecular docking studies of some new quinoxaline derivatives targeting dihyropteroate synthase enzyme
| Autor: | Abeer E. Abdel Wahab, Ibrahim A. Abdelwahab, Rasha Y. Elbayaa, Soad A.M. El-Hawash, Maryam A.Z. El-Attar, Omaima G. Shaaban, Nargues S. Habib |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Yersinia pestis
DHPS Levofloxacin Microbial Sensitivity Tests Gram-Positive Bacteria 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Quinoxaline Thiadiazoles Catalytic Domain Quinoxalines Gram-Negative Bacteria Drug Discovery Pterin Molecular Biology Dihydropteroate Synthase Molecular Structure 010405 organic chemistry Organic Chemistry Hydrogen Bonding Antimicrobial Combinatorial chemistry Anti-Bacterial Agents 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry chemistry Docking (molecular) Drug Design Antibacterial activity Dihydropteroate synthase Hydrophobic and Hydrophilic Interactions Protein Binding |
| Zdroj: | Bioorganic Chemistry. 76:437-448 |
| ISSN: | 0045-2068 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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