Phytochemicals as Inhibitors of Bacterial Cell Division Protein FtsZ: Coumarins Are Promising Candidates
| Autor: | Rakesh P. Nankar, Selvakumar Rajendran, Sridevi Duggirala, Mukesh Doble |
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| Rok vydání: | 2014 |
| Předmět: |
Cell division
Stereochemistry bacterial protein cytoskeleton protein daphnetin FtsZ protein Bacteria scopoletin umbelliferone derivative 3T3 cell line animal antagonists and inhibitors Bacillus subtilis cell division chemistry drug effects Escherichia coli growth development and aging human mouse Animals Bacterial Proteins Cell Division Cytoskeletal Proteins Humans Mice NIH 3T3 Cells Scopoletin Umbelliferones Bioengineering medicine.disease_cause Applied Microbiology and Biotechnology Biochemistry chemistry.chemical_compound medicine heterocyclic compounds FtsZ Cytotoxicity Molecular Biology biology General Medicine biology.organism_classification Docking (molecular) biology.protein Antibacterial activity Biotechnology |
| Zdroj: | Applied Biochemistry and Biotechnology. 174:283-296 |
| ISSN: | 1559-0291 0273-2289 |
| DOI: | 10.1007/s12010-014-1056-2 |
| Popis: | Naturally occurring phytochemicals with reported antibacterial activity were screened for their ability to inhibit the bacterial cell division protein Escherichia coli FtsZ. Among the representative compounds, coumarins inhibit the GTPase and polymerization activities of this protein effectively. Further screening with ten coumarin analogs we identified two promising candidates, scopoletin and daphnetin. The former is found to inhibit the GTPase activity of the protein in a noncompetitive manner. Docking of these coumarins with the modeled protein indicate that they bind to T7 loop, which is different from the GTP-binding site (active site), thereby supporting the experimental data. Lowest binding energy is obtained with scopoletin. 3D QSAR indicates the need for groups such as hydroxyl, diethyl, or dimethyl amino in the 7th carbon for enhanced activity. None of the coumarins exhibited cytotoxicity against NIH/3T3 and human embryonic kidney cell lines. The length of Bacillus subtilis increases in the presence of these compounds probably due to the lack of septum formation. Results of this study indicate the role of coumarins in halting the first step of bacterial cell division process. |
| Databáze: | OpenAIRE |
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