Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Biofilm Inhibition
2.3. Molecular Docking Studies
2.4. Molecular Dynamics Simulations
3. Discussion
4. Materials and Methods
4.1. Chemistry
4.2. Evaluation of Biofilm Inhibition
4.3. Inhibition of Pyocyanin Formation
4.4. Molecular Docking
4.5. Molecular Dynamics Simulations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 3a-i and 4a-i are available from the authors. |
BI (%) (±s.d.) | BI (%) (±s.d.) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Cmp | n | S.a | P.a | PEI | Cmp | n | S.a | P.a | PEI |
3a | 1 | 15.3 (±2.8) | 26.4 (±4.6) | 1.22 | 4a | 1 | < 5 | 28.65 (±2.2) | 1.24 |
3b | 2 | 31.2 (±3.6) | 30.6 (±3.9) | 1.33 | 4b | 2 | 29.8 (±5.1) | 29.43 (±3.1) | 1.20 |
3c | 3 | <5 | 37.5 (±2.6) | 1.54 | 4c | 3 | <5 | 33.09 (±3.2) | 1.28 |
3d | 4 | <5 | 36.6 (±1.7) | 1.42 | 4d | 4 | <5 | 44.95 (±1.6) | 1.64 |
3e | 6 | 22.6 (±5.7) | 43.8 (±3.4) | 1.53 | 4e | 6 | <5 | 48.97 (±4.6) | 1.62 |
3f | 8 | 24.8 (±1.5) | 50.6 (±4.0) | 1.61 | 4f | 8 | 11.9 (±4.2) | 53.38 (±2.5) | 1.62 |
3g | 10 | 18.0 (±1.2) | 54.2 (±4.0) | 1.46 | 4g | 10 | 15.7 (±5.8) | 61.45 (±2.2) | 1.72 |
3h | 12 | 25.7 (±1.1) | 52.3 (±4.2) | 1.41 | 4h | 12 | 16.8 (±4.4) | 57.63 (±3.2) | 1.49 |
3i | 14 | 34.7 (±2.0) | 49.8 (±1.8) | 1.25 | 4i | 14 | 14.2 (±5.4) | 56.62 (±3.1) | 1.37 |
MolDock Score | MolDock Score | ||||||||
---|---|---|---|---|---|---|---|---|---|
Ligand | BI (%) | PqsD | LasR | logP | Ligand | BI (%) | PqsD | LasR | logP |
3a | 26.36 | −99.478 | −101.21 | 2.53 | 4a | 28.65 | −96.4705 | −104.98 | 1.11 |
3b | 30.61 | −103.646 | −109.25 | 3.06 | 4b | 29.43 | −104.784 | −110.48 | 1.64 |
3c | 37.54 | −105.508 | −113.46 | 3.59 | 4c | 33.09 | −110.356 | −116.89 | 2.17 |
3d | 36.56 | −111.982 | −114.62 | 4.12 | 4d | 44.95 | −117.802 | −125.21 | 2.70 |
3e | 43.84 | −125.746 | −137.16 | 5.18 | 4e | 48.97 | −129.125 | −142.73 | 3.76 |
3f | 50.57 | −131.982 | −152.30 | 6.24 | 4f | 53.38 | −136.142 | −145.82 | 4.82 |
3g | 54.20 | −124.547 | −151.66 | 6.77 | 4g | 61.45 | −139.494 | −152.81 | 5.35 |
3h | 52.27 | −125.681 | −146.32 | 7.30 | 4h | 57.63 | −133.275 | −159.79 | 5.88 |
3i | 49.82 | −147.112 | −156.07 | 7.83 | 4i | 56.62 | −150.072 | −181.92 | 6.41 |
LasR | PqsD | |||||
---|---|---|---|---|---|---|
Average RMSD (Å) | LBE (KJ/mol) | GE 2 | Average RMSD (Å) | LBE (KJ/mol) | GE 2 | |
4a | 1.79 | 7.09 | -- | 2.55 | 75.69 | -- |
4g | 2.01 | 2.01 | −0.56 | 2.38 | 200.44 | 13.86 |
4i | 1.70 | −11.26 | −1.41 | 2.37 | 229.30 | 11.81 |
AHL | 1.76 | 3.29 | -- | 3.26 | ---- | -- |
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Espinosa-Valdés, M.P.; Borbolla-Alvarez, S.; Delgado-Espinosa, A.E.; Sánchez-Tejeda, J.F.; Cerón-Nava, A.; Quintana-Romero, O.J.; Ariza-Castolo, A.; García-Del Río, D.F.; Loza-Mejía, M.A. Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors. Molecules 2019, 24, 327. https://doi.org/10.3390/molecules24020327
Espinosa-Valdés MP, Borbolla-Alvarez S, Delgado-Espinosa AE, Sánchez-Tejeda JF, Cerón-Nava A, Quintana-Romero OJ, Ariza-Castolo A, García-Del Río DF, Loza-Mejía MA. Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors. Molecules. 2019; 24(2):327. https://doi.org/10.3390/molecules24020327
Chicago/Turabian StyleEspinosa-Valdés, Mariana Paola, Sara Borbolla-Alvarez, Ana Elena Delgado-Espinosa, Juan Francisco Sánchez-Tejeda, Anabelle Cerón-Nava, Osvaldo Javier Quintana-Romero, Armando Ariza-Castolo, Diego Fernando García-Del Río, and Marco A. Loza-Mejía. 2019. "Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors" Molecules 24, no. 2: 327. https://doi.org/10.3390/molecules24020327
APA StyleEspinosa-Valdés, M. P., Borbolla-Alvarez, S., Delgado-Espinosa, A. E., Sánchez-Tejeda, J. F., Cerón-Nava, A., Quintana-Romero, O. J., Ariza-Castolo, A., García-Del Río, D. F., & Loza-Mejía, M. A. (2019). Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors. Molecules, 24(2), 327. https://doi.org/10.3390/molecules24020327