1. Novel coumarin-pyrazole carboxamide derivatives as potential topoisomerase II inhibitors: Design, synthesis and antibacterial activity
- Author
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Wei Wang, Ming-Jie Chu, Xian-Hai Lv, Zi-Li Ren, Jie-Xiu Gong, Quan-Wei Ma, Hao Liu, and Jie-Chun Wang
- Subjects
Staphylococcus aureus ,medicine.drug_class ,Stereochemistry ,Carboxamide ,Pyrazole ,medicine.disease_cause ,01 natural sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,Coumarins ,Salmonella ,Drug Discovery ,medicine ,Escherichia coli ,Humans ,Topoisomerase II Inhibitors ,Pharmacology ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Topoisomerase ,Organic Chemistry ,General Medicine ,Coumarin ,Listeria monocytogenes ,0104 chemical sciences ,Anti-Bacterial Agents ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,DNA Topoisomerases, Type II ,Drug Design ,biology.protein ,Pyrazoles ,Topoisomerase-II Inhibitor ,Antibacterial activity - Abstract
The identification of novel Topoisomerase II (Topo II) inhibitors is one of the most attractive directions in the field of bactericide research and development. In our ongoing efforts to pursue the class of inhibitors, six series of 70 novel coumarin-pyrazole carboxamide derivatives were designed and synthesized. As a result of the evaluation against four destructive bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella. Compound 8III-k (MIC = 0.25 mg/L) showed considerable inhibitory activity than ciprofloxacin (MIC = 0.5 mg/L) against Escherichia coli and 8V-c (MIC = 0.05 mg/L) exhibited excellent antibacterial activity than ciprofloxacin (MIC = 0.25 mg/L) against Salmonella. The selected compounds (8III-k, 8V-c and 8V-k) exhibit potent inhibition against Topo II and Topo IV with IC50 values (9.4–25 mg/L). Molecular docking model showed that the compounds 8V-c and 8V-k can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial Topo II inhibiting bactericides.
- Published
- 2018