Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.1.1. Synthesis
2.1.2. Quantum Chemical Calculations
2.2. Biological Studies
2.2.1. Anti-Biofilm Activity of Benzofuroxan Derivatives
2.2.2. Fungistatic Activity of Benzofuroxans
2.2.3. Cytotoxicity of Test Compounds Toward Cancer and Normal Human Cell Lines
2.2.4. Induction of Apoptotic Effects by Test Compounds
2.2.5. Effects on the Mitochondrial Membrane Potential (ΔΨm)
2.2.6. Cell Cycle Analysis
3. Materials and Methods
3.1. Chemistry
3.2. Biological Studies
3.2.1. Bacterial Biofilm Formation Inhibitory Activity
3.2.2. Fungistatic Activity of Benzofuroxans
3.2.3. Cytotoxicity Assay
3.2.4. Flow Cytometry Assay
3.2.5. Mitochondrial Membrane Potential
3.2.6. Cell Cycle Analysis
3.2.7. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Reaction Products | ΔE | ΔH | ΔG |
---|---|---|---|
Pa + HCl | 9.91 | 11.13 | 8.21 |
Pb + HCl | 2.32 | 3.70 | 1.37 |
ΔE | ΔH | ΔG | HOMO-LUMO | |
---|---|---|---|---|
1 + A* | 0.00 | 0.00 | 0.00 | – |
R(1 + A)a | −3.41 | −2.09 | 5.69 | – |
R(1 + A)b | −3.20 | −1.90 | 6.46 | – |
WM1 | 15.02 | 16.28 | 30.80 | 3.10 |
WM2 | 29.61 | 30.75 | 44.41 | 2.13 |
Pa + HCl | −9.91 | −11.13 | −8.21 | 2.99 |
Pb + HCl | −2.32 | −3.70 | −1.37 | 2.86 |
Compound | Biofilm Formation, % | |||||
---|---|---|---|---|---|---|
Compound Concentration, M | ||||||
1 × 10−9 | 1 × 10−8 | 1 × 10−7 | 1 × 10−6 | 1 × 10−5 | 1 × 10−4 | |
3a | 104.09 | 81.39 | 51.29 * | 104.19 * | 116.74 | 108.56 * |
3b | 29.56 * | 18.75 * | 49.17 * | 98.92 | 46.33 * | 5.78 * |
3c | 83.88 | 22.91 * | 67.33 * | 91.23 | 121.82 * | 6.23 * |
3d | 15.18 * | 11.69 * | 57.03 * | 100.31 | 63.01 * | 118.72 * |
3e | 85.02 | 85.82 | 41.01 * | 96.34 | 65.93 * | 94.48 * |
3f ** | 66.58 | 9.31 * | 11.34 * | 43.56 * | 96.57 | 98.97 |
5b | 88.50 | 25.54 * | 37.51 * | 88.43 * | 92.32 | 100.88 |
5e | 26.21 * | 21.15 * | 70.11 * | 96.38 | 116.36 | 110.85 * |
5f | 25.67 * | 26.88 * | 63.58 * | 96.08 | 96.24 | 103.47 |
5g | 45.78 * | 22.40 * | 27.37 * | 79.81 * | 108.84 | 107.18 |
Azithromycin | 103.42 | 102.43 | 99.39 | 103.80 | 81.50 * | 103.42 |
Test Compound | Cancer Cell Lines | Normal Cell Lines | |||||||
---|---|---|---|---|---|---|---|---|---|
M-HeLa | MCF7 | PANC-1 | T98G | Chang Liver | |||||
IC50 | SI | IC50 | SI | IC50 | SI | IC50 | SI | ||
3a | 45.9 ± 3.7 | 2.0 | >100 | n.s. | >100 | n.s | 28.3 ± 2.3 | 3.3 | 93.8 ± 8.3 |
3b | 60.6 ± 4.7 | 1.0 | 69.2 ± 5.7 | n.s. | 82.7 ± 7.3 | n.s | 12.7 ± 1.1 | 5.0 | 62.7 ± 5.5 |
3c | 4.8 ± 0.4 | 12.8 | 3.7 ± 0.2 | 16.6 | 59.2 ± 4.6 | 1.0 | 20.4 ± 1.7 | 3 | 61.3 ± 5.1 |
3d | 16.6 ± 1.4 | >6 | 67.9 ± 5.7 | >1.5 | 61.3 ± 5.1 | >1.6 | 14.7 ± 1.2 | >6.8 | >100 |
3e | 62.7 ± 5.4 | 1.0 | 79.5 ± 6.4 | n.s. | 50.0 ± 4.1 | 1.3 | 21.5 ± 1.8 | 3.0 | 62.7 ± 5.6 |
3f | 16.0 ± 1.3 | 4.0 | 8.1 ± 0.7 | 8.0 | >100 | n.s. | 59.8 ± 4.8 | 1.1 | 64.4 ± 5.7 |
5a | 56.5 ± 4.5 | 1.8 | >100 | n.s. | >100 | n.s. | 22.7 ± 1.9 | 4.4 | 100 |
5b | 60.8 ± 4.8 | >1.6 | >100 | n.s. | 50.0 ± 3.9 | >2 | 65.0 ± 5.8 | >1.5 | >100 |
5c | 49.3 ± 3.9 | >2 | >100 | n.s. | 38 ± 2.9 | >2.6 | >100 | n.s. | >100 |
5d | 61.0 ± 5.2 | 1.1 | 79.1 ± 6.2 | n.s. | >100 | n.s. | 31.6 ± 2.5 | 2.1 | 67.1 ± 5.7 |
5e | 61.6 ± 5.2 | 1.1 | >100 | n.s. | >100 | n.s. | 57.1 ± 4.3 | 1.1 | 65.2 ± 5.8 |
5f | 62.2 ± 5.6 | >1.6 | >100 | n.s. | >100 | n.s. | >100 | n.s. | >100 |
5g | >100 | n.s. | >100 | n.s. | >100 | n.s. | >100 | n.s. | >100 |
Doxorubicin | 3.0 ± 0.1 | 1.0 | 3.0 ± 0.2 | 1.0 | 3.3 ± 0.1 | 1.0 | 6.8 ± 0.5 | n.s. | 3.0 ± 0.2 |
Tamoxifen | 28 ± 2.5 | 1.5 | 25 ± 2.2 | 1.7 | – | 42.1 ± 3.5 |
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Chugunova, E.; Gazizov, A.; Sazykina, M.; Akylbekov, N.; Gildebrant, A.; Sazykin, I.; Burilov, A.; Appazov, N.; Karchava, S.; Klimova, M.; et al. Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity. Int. J. Mol. Sci. 2020, 21, 8292. https://doi.org/10.3390/ijms21218292
Chugunova E, Gazizov A, Sazykina M, Akylbekov N, Gildebrant A, Sazykin I, Burilov A, Appazov N, Karchava S, Klimova M, et al. Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity. International Journal of Molecular Sciences. 2020; 21(21):8292. https://doi.org/10.3390/ijms21218292
Chicago/Turabian StyleChugunova, Elena, Almir Gazizov, Marina Sazykina, Nurgali Akylbekov, Anastasiya Gildebrant, Ivan Sazykin, Alexander Burilov, Nurbol Appazov, Shorena Karchava, Maria Klimova, and et al. 2020. "Design of Novel 4-Aminobenzofuroxans and Evaluation of Their Antimicrobial and Anticancer Activity" International Journal of Molecular Sciences 21, no. 21: 8292. https://doi.org/10.3390/ijms21218292