Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Finding Potential MCR-1 Inhibitors by Virtual Screening
2.2. Evaluation of the Activity of Potential MCR-1 Inhibitors
2.3. Compound Design
2.4. Chemistry
2.5. Activity Evaluation and SAR Study
2.6. Inhibitory Effects Against MCR-1
2.7. Molecular Docking
3. Materials and Methods
3.1. Structure-Based Virtual Screening
3.2. Chemistry
3.3. Biological Assay
3.3.1. Determination of the MIC of Colistin
3.3.2. The Susceptibility Testing of Colistin Combined with Compounds
3.3.3. The Assay for MCR-1 Enzymatic Activity
3.4. Molecular Docking
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
E. coli BL21(DE3) Strains | Colistin MIC (μg·mL−1) |
---|---|
BL21(DE3) | 2 |
pET28a | 2 |
pET28a-mcr-1 | 8 |
Comp. | R1 | R2 | R3 | R4 | R5 | Conc. (μM) |
---|---|---|---|---|---|---|
3 | | H | H | | | 100 |
6a | | H | H | | | N.I.A. |
6b | | H | H | | | N.I.A. |
6c | | H | | | | N.I.A. |
6d | | H | H | | | N.I.A. |
6e | | H | H | | | N.I.A. |
6f | | H | H | | | N.I.A. |
6g | | H | H | | | 50 |
6h | | H | H | | | 50 |
6i | | H | H | | | 50 |
6j | | H | H | | | N.I.A. |
6k | | H | H | | | N.I.A. |
6l | | H | H | | | N.I.A. |
6m | | H | H | | | N.I.A. |
6n | | H | H | | | 50 |
6o | | H | | | | 100 |
6p | | | H | | | 25 |
6q | | H | H | | | 25 |
6r | | H | | | | 50 |
Comp. | Conc. (μM) | Comp. | Conc. (μM) |
---|---|---|---|
8a | N.I.A. | 9a | N.I.A. |
8b | N.I.A. | 9b | N.I.A. |
8c | N.I.A. | 9c | N.I.A. |
8d | N.I.A. | 9d | N.I.A. |
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Share and Cite
Lan, X.-j.; Yan, H.-t.; Lin, F.; Hou, S.; Li, C.-c.; Wang, G.-s.; Sun, W.; Xiao, J.-h.; Li, S. Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors. Molecules 2019, 24, 2719. https://doi.org/10.3390/molecules24152719
Lan X-j, Yan H-t, Lin F, Hou S, Li C-c, Wang G-s, Sun W, Xiao J-h, Li S. Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors. Molecules. 2019; 24(15):2719. https://doi.org/10.3390/molecules24152719
Chicago/Turabian StyleLan, Xiu-juan, Hai-tao Yan, Feng Lin, Shi Hou, Chen-chen Li, Guang-shu Wang, Wei Sun, Jun-hai Xiao, and Song Li. 2019. "Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors" Molecules 24, no. 15: 2719. https://doi.org/10.3390/molecules24152719