Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans
Abstract
:1. Introduction
2. Results and Discussion
2.1. Cytostatic Activity against Tumor Cell Lines
IC50a (µM) | BIC50b (µM) | TI cS. Typhimurium | TI P. aeruginosa | C. elegans | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n° | R4 | R1 | R2 | R3 | L1210 | CEM | HeLa | S. Typhimurium | P. aeruginosa | L1210 | CEM | HeLa | L1210 | CEM | HeLa | % survival at 25 µM e | |||
monosubstituted | |||||||||||||||||||
1 | H | H | H | H | 62.9 | 94.3 | 144.6 | 130.2 | 72.6 | 0.5 | 0.7 | 1.1 | 0.9 | 1.3 | 2.0 | 89.8 | |||
2 | 4-Cl | H | H | H | 77.5 | 49.6 | 72.3 | 16 | 3.5 | 4.8 | 3.1 | 4.5 | 22.1 | 14.2 | 20.7 | 84.9 | |||
3 | 4-Ph | H | H | H | 37.4 | 13.6 | 34.0 | 17.3 | 8.6 | 2.2 | 0.8 | 2.0 | 4.3 | 1.6 | 4.0 | nd | |||
4 | 4-NO2 | H | H | H | 83.3 | 63.7 | 107.7 | 17.6 | 34.5 | 4.7 | 3.6 | 6.1 | 2.4 | 1.8 | 3.1 | 97.3 | |||
5 | 4-Br | H | H | H | 10.1 | 13.9 | 21.8 | 47.9 | 3.2 | 0.2 | 0.3 | 0.5 | 3.2 | 4.3 | 6.8 | 90.6 | |||
N1-substituted | |||||||||||||||||||
6 | H | Oct | H | H | 3.2 | 467.9 | 3.0 | 11.9 | 18.5 | 0.3 | 39.3 | 0.3 | 0.2 | 25.3 | 0.2 | 92.5 | |||
7 | 4-Cl | Oct | H | H | 3.9 | 356.8 | 4.5 | 5.9 | 4.0 | 0.7 | 60.5 | 0.8 | 1.0 | 89.2 | 1.1 | 86.6 | |||
8 | 4-Cl | Trd | H | H | 7.2 | 6.4 | 4.5 | 19.5 | 33.9 | 0.4 | 0.3 | 0.2 | 0.2 | 0.2 | 0.1 | nd | |||
9 | 4-Ph | Hept | H | H | 7.5 | 8.1 | 8.7 | 9.3 | 25.2 | 0.8 | 0.9 | 0.9 | 0.3 | 0.3 | 0.3 | nd | |||
10 | 4-Ph | Oct | H | H | 7.8 | 8.3 | 6.6 | 3.3 | 8.9 | 2.4 | 2.5 | 2.0 | 0.9 | 0.9 | 0.7 | nd | |||
11 | 4-Ph | c-Pen | H | H | 4.3 | 2.9 | 8.2 | 7.5 | 353.1 | 0.6 | 0.4 | 1.1 | 0.01 | 0.01 | 0.02 | nd | |||
12 | 4-Ph | c-Hept | H | H | 8.1 | 5.4 | 6.6 | 12.5 | 6.6 | 0.6 | 0.4 | 0.5 | 1.2 | 0.8 | 1.0 | nd | |||
13 | 4-Ph | c-Oct | H | H | 6.9 | 4.9 | 6.9 | 22.9 | 3.2 | 0.3 | 0.2 | 0.3 | 2.2 | 1.5 | 2.2 | nd | |||
14 | 4-F | Oct | H | H | 3.5 | 7.3 | 8.6 | 10.8 | 4.9 | 0.3 | 0.7 | 0.8 | 0.7 | 1.5 | 1.8 | nd | |||
15 | 4-SMe | Oct | H | H | 4.1 | 7.2 | 6.3 | 6.7 | 2.8 | 0.6 | 1.1 | 0.9 | 1.5 | 2.6 | 2.3 | nd | |||
16 | 3-Br | Oct | H | H | 6.9 | 9.7 | 8.0 | 11.2 | 40.6 | 0.6 | 0.9 | 0.7 | 0.2 | 0.2 | 0.2 | nd | |||
17 | 3,4-diCl | m-MeOPhenethyl | H | H | 6.9 | 8.6 | 6.6 | >400 | nd d | <0.02 | <0.02 | <0.02 | nd | nd | nd | nd | |||
2N-substituted | |||||||||||||||||||
18 | H | H | Bu | H | 46.4 | 667.4 | 19.5 | 25.3 | 31.8 | 1.8 | 26.4 | 0.8 | 1.5 | 21.0 | 0.6 | nd | |||
19 | H | H | i-Bu | H | 83.6 | 382.7 | 91.4 | 4.9 | 1.2 | 17.1 | 78.1 | 18.7 | 69.7 | 318.9 | 76.2 | nd | |||
20 | H | H | c-Pen | H | 27.3 | 293.3 | 27.3 | 52.9 | 33.8 | 0.5 | 5.5 | 0.5 | 0.8 | 8.7 | 0.8 | 98.1 | |||
21 | 4-Cl | H | Bu | H | 40.0 | 374.6 | 34.7 | nd | nd | nd | nd | nd | nd | nd | nd | nd | |||
22 | 4-Cl | H | i-Bu | H | 336.3 | 297.3 | 171.5 | 2 | 0.9 | 168.2 | 148.7 | 85.8 | 373.7 | 330.3 | 190.6 | 97.6 | |||
23 | 4-Cl | H | Pen | H | 22.0 | 322.9 | 19.8 | >400 | 6.3 | <0.05 | <0.8 | <0.05 | 3.5 | 51.3 | 3.1 | nd | |||
24 | 4-Cl | H | c-Pen | H | 35.5 | 591.0 | 28.8 | 4.4 | 13.5 | 8.1 | 134.3 | 6.5 | 2.6 | 43.8 | 2.1 | 100.1 | |||
25 | 4-Br | H | Bu | H | 125.8 | 493.0 | 50.7 | 7.1 | 9.8 | 17.7 | 69.4 | 7.1 | 12.8 | 50.3 | 5.2 | 102.4 | |||
26 | 4-Br | H | i-Bu | H | 31.7 | 306.0 | 22.6 | 2.9 | 1.2 | 10.9 | 105.5 | 7.8 | 26.4 | 255.0 | 18.8 | nd | |||
27 | 4-Br | H | Pen | H | 14.9 | 375.2 | 16.3 | 3.1 | 10.2 | 4.8 | 121.0 | 5.2 | 1.5 | 36.8 | 1.6 | nd | |||
28 | 4-Br | H | c-Pen | H | 32.7 | 673.6 | 32.7 | 12.1 | 7.2 | 2.7 | 55.7 | 2.7 | 4.5 | 93.6 | 4.5 | nd | |||
29 | 3,4-diCl | H | c-Pen | H | 76.1 | 155.9 | 79.8 | 5.7 | 7.9 | 13.4 | 27.4 | 14.0 | 9.6 | 19.7 | 10.1 | nd | |||
4,5-disubstituted | |||||||||||||||||||
30 | H | H | H | 4-OMePh | 64.1 | 52.8 | 45.2 | 77.1 | nd | 0.8 | 0.7 | 0.6 | nd | nd | nd | nd | |||
31 | H | H | H | 4-ClPh | 59.3 | 48.2 | 40.8 | 46.9 | nd | 1.3 | 1.0 | 0.9 | nd | nd | nd | nd | |||
32 | 4-Cl | H | H | 4-MePh | 12.3 | 10.2 | 9.5 | 12.9 | nd | 1.0 | 0.8 | 0.7 | nd | nd | nd | nd | |||
33 | 4-Cl | H | H | 4-CF3Ph | 41.5 | 35.5 | 26.1 | 10.8 | nd | 3.8 | 3.3 | 2.4 | nd | nd | nd | nd | |||
34 | 4-F | H | H | amidophenyl | 74.2 | 74.2 | 77.6 | 182.1 | nd | 0.4 | 0.4 | 0.4 | nd | nd | nd | nd | |||
1,4,5-trisubstituted | |||||||||||||||||||
35 | 4-Me | Ben | H | p-PenOBn | 8.6 | 8.4 | 14.8 | 10.3 | 27.4 | 0.8 | 0.8 | 1.4 | 0.3 | 0.3 | 0.5 | nd | |||
2AI-triazole conjugates | |||||||||||||||||||
36 | H | H | n = 2, R'= Ph | H | 221.0 | 452.6 | 72.9 | 36.5 | >400 | 6.1 | 12.4 | 2.0 | <0.6 | <1.1 | <0.2 | 87.7 | |||
37 | H | H | n = 3, R' = Ph | H | 217.8 | 459.2 | 106.7 | 40.0 | 19.0 | 5.4 | 11.5 | 2.7 | 11.5 | 24.2 | 5.6 | 86.4 | |||
38 | 4-OMe | H | n = 2, R' = 4-BrPh | H | 18.4 | 596.6 | 16.8 | 91.2 | 42.7 | 0.2 | 6.5 | 0.2 | nd | nd | nd | nd | |||
39 | 4-Br | H | n = 2, R' = c-Hex | H | 20.7 | 396.0 | 22.5 | 8.4 | 12.5 | 2.5 | 47.1 | 2.7 | 1.7 | 31.7 | 1.8 | 99.3 | |||
40 | 4-Br | H | n = 2, R' = c-Pr | H | 43.9 | 33.6 | 67.1 | 2.0 | 71.6 | 21.9 | 16.8 | 33.6 | 0.6 | 0.5 | 0.9 | 82.6 |
2.2. Effects on Viability and Functional Behavior of Bone Cells
2.3. Evaluation of the Toxicity against C. elegans
3. Experimental Section
3.1. Compound Preparation
3.2. Cytostatic Activity against Tumor Cell Lines
3.3. Cytotoxicity against Osteoblasts and Mesenchymal Stem Cells
3.4. Calcium Assay for Determination of Osteogenic Differentiation Potential
3.5. C. elegans Toxicity Test
4. Conclusions
Supplementary Materials
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interest
References
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Steenackers, H.; Dubey, A.; Robijns, S.; Ermolat'ev, D.; Delattin, N.; Dovgan, B.; Girandon, L.; Fröhlich, M.; De Brucker, K.; Cammue, B.P.A.; et al. Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans. Molecules 2014, 19, 16707-16723. https://doi.org/10.3390/molecules191016707
Steenackers H, Dubey A, Robijns S, Ermolat'ev D, Delattin N, Dovgan B, Girandon L, Fröhlich M, De Brucker K, Cammue BPA, et al. Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans. Molecules. 2014; 19(10):16707-16723. https://doi.org/10.3390/molecules191016707
Chicago/Turabian StyleSteenackers, Hans, Akanksha Dubey, Stijn Robijns, Denis Ermolat'ev, Nicolas Delattin, Barbara Dovgan, Lenart Girandon, Mirjam Fröhlich, Katrijn De Brucker, Bruno P. A. Cammue, and et al. 2014. "Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans" Molecules 19, no. 10: 16707-16723. https://doi.org/10.3390/molecules191016707
APA StyleSteenackers, H., Dubey, A., Robijns, S., Ermolat'ev, D., Delattin, N., Dovgan, B., Girandon, L., Fröhlich, M., De Brucker, K., Cammue, B. P. A., Thevissen, K., Balzarini, J., Van der Eycken, E. V., & Vanderleyden, J. (2014). Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans. Molecules, 19(10), 16707-16723. https://doi.org/10.3390/molecules191016707