Selectively Halogenated Flavonolignans—Preparation and Antibacterial Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Activity
2.2.1. Inhibition of Bacterial Communication
2.2.2. Effect on Biofilm Formation
2.2.3. Modulation of Antibiotic-Resistant Phenotype in Resistant Bacteria
2.2.4. Antioxidant Capacity, Reducing Potential and Lipoperoxidation Inhibition
2.2.5. Cytotoxicity and Anti-Inflammatory Activity
3. Materials and Methods
3.1. General Experimental Procedures
3.2. General Procedure A for Tribromination
3.3. General Procedure B for Diiodination
3.4. General Procedure C for Chlorination
3.5. General Procedure D for Selective Dehalogenation
3.6. Inhibition of Quorum Sensing
3.7. Sensitization of Antibiotic-Resistant Bacteria
3.8. Inhibition of Biofilm Formation and Disruption of Maturated Biofilm
3.9. Antioxidant Activity, Reducing Potential, and Lipid Peroxidation Inhibition
3.10. Cytotoxicity
3.11. Inhibition of Nitric Oxide Production
3.12. Sensitization of Doxorubicin-Resistant Human Ovarian Carcinoma Cells
3.13. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Vibrio campbellii BAA 1118 (AI-1) | Vibrio campbellii BAA 1119 (AI-2) | |||||||
---|---|---|---|---|---|---|---|---|
EC50 [µM] | IC50 [µM] | SI | SA $ | EC50 [µM] | IC50 [µM] | SI | SA $ | |
Taxifolin (1) | 63.7 ± 2.7 | 71.0 ± 3.0 | 1.1 ± 0.1 | E | 7.3 ± 0.3 | 80.0 ± 1.7 | 11.0 ± 0.6 | A |
6-Bromotaxifolin (7) | 38.9 ± 1.6 | 59.0 ± 0.1 | 1.5 ± 0.1 | * | 11.9 ± 0.5 | 19.7 ± 1.0 | 1.7 ± 0.2 | *** |
6,8-Dibromotaxifolin (8) | 38.1 ± 2.0 | 55.5 ± 1.0 | 1.5 ± 0.1 | * | 10.1 ± 0.4 | 109.3 ± 0.8 | 10.8 ± 0.6 | |
Quercetin (2) | 15.9 ± 0.5 | 24.5 ± 0.8 | 1.5 ± 0.1 | C, D | 4.8 ± 0.2 | 10.6 ± 0.5 | 2.2 ± 0.2 | C |
8-Bromoquercetin (9) | 25.6 ± 0.5 | 27.8 ± 0.5 | 1.08 ± 0.04 | ***** | 0.4 ± 0.02 | 1.1 ± 0.1 | 2.9 ± 0.3 | ***** |
6,8-Dibromoquercetin (10) | 7.3 ± 0.4 | 13.8 ± 0.5 | 1.9 ± 0.2 | ** | 0.7 ± 0.02 | 3.5 ± 0.1 | 5.0 ± 0.3 | ** |
Silybin A (3a) | 97.1 ± 1.0 | 131.0 ± 3.7 | 1.3 ± 0.1 | D | 17.1 ± 0.5 | 119.6 ± 3.1 | 7.0 ± 0.4 | B |
6-Bromosilybin A (11) | 24.4 ± 0.7 | 51.7 ± 0.7 | 2.1 ± 0.1 | ***** | 9.4 ± 0.5 | 51.5 ± 0.6 | 5.5 ± 0.3 | * |
8-Bromosilybin A (19) | 33.9 ± 1.8 | 114.9 ± 5.4 | 3.4 ± 0.3 | *** | 4.6 ± 0.3 | >200 | ≥43.1 ± 2.6 | *** |
6,8-Dibromosilybin A (12) | 12.2 ± 0.4 | 23.5 ± 1.0 | 1.9 ± 0.2 | *** | 13.2 ± 0.3 | 80.5 ± 4.8 | 6.1 ± 0.5 | |
6,8,21-Tribromosilybin A (21) | >200 | >200 | 30.7 ± 1.6 | >200 | ≥6.5 ± 0.3 | |||
Silybin B (3b) | 121.5 ± 0.6 | 116.6 ± 0.9 | 0.96 ± 0.01 | E | 22.3 ± 0.5 | 152.4 ± 2.4 | 6.8 ± 0.2 | B |
6-Bromosilybin B (13) | 14.5 ± 0.5 | 16.1 ± 0.1 | 1.11 ± 0.04 | * | 26.1 ± 1.3 | 52.7 ± 0.6 | 2.0 ± 0.1 | ***** |
6-Chlorosilybin B (28) | 114.2 ± 5.0 | 130.1 ± 5.9 | 1.1 ± 0.1 | 3.2 ± 0.2 | >200 | ≥62.6 ± 3.6 | *** | |
8-Bromosilybin B (20) | 44.2 ± 0.7 | 126.6 ± 4.0 | 2.9 ± 0.1 | *** | 4.7 ± 0.2 | 200 | ≥42.9 ± 2.1 | *** |
6,8-Dibromosilybin B (14) | 14.7 ± 0.7 | 16.6 ± 0.8 | 1.1 ± 0.1 | 19.3 ± 0.5 | 60.2 ± 3.4 | 3.1 ± 0.3 | ***** | |
6,8,21-Tribromosilybin B (22) | 4.3 ± 0.3 | 7.3 ± 0.1 | 1.7 ± 0.1 | * | 12.0 ± 0.5 | 34.4 ± 1.8 | 2.9 ± 0.3 | **** |
2,3-Dehydrosilybin AB (4) | 59.9 ± 2.0 | 163.2 ± 3.8 | 2.7 ± 0.2 | A | 10.2 ± 0.4 | 25.3 ± 1.0 | 2.5 ± 0.2 | C |
8-Bromo-2,3-dehydrosilybin AB (16) | >200 | >200 | 6.9 ± 0.3 | 87.0 ± 2.5 | 12.7 ± 1.0 | ***** | ||
6,8-Dibromo-2,3-dehydrosilybin AB (17) | 55.5 ± 1.6 | >200 | ≥3.6 ± 0.1 | *** | 4.1 ± 0.2 | 126.8 ± 7.4 | 31.2 ± 3.5 | **** |
Silychristin A (5) | >200 | >200 | >200 | >200 | ||||
6,8-Dibromosilychristin A (15) | >200 | >200 | >200 | >200 | ||||
2,3-dehydrosilychristin A (6) | 22.3 ± 1.0 | 43.0 ± 1.5 | 1.9 ± 0.2 | B | 11.1 ± 0.1 | 11.0 ± 0.4 | 0.99 ± 0.05 | D |
8-Bromo-2,3-dehydrosilychristin A (18) | 29.4 ± 0.7 | 80.1 ± 1.7 | 2.7 ± 0.1 | ** | 10.5 ± 0.2 | 23.0 ± 0.2 | 2.2 ± 0.1 | ***** |
5-Fluorouracil (PC) | (0.39 ± 0.05) × 10−3 | (0.68 ± 0.01) × 10−3 | 1.73 ± 0.05 | B, C | (0.44 ± 0.03) × 10−3 | (3.41 ± 0.03) × 10−3 | 7.8 ± 0.5 | B |
Pseudomonas aeruginosa | Staphylococcus aureus | |||
---|---|---|---|---|
Imipenem | Colistin | Chloramphenicol | Gentamicin | |
4 mg/L | 2 mg/L | 8 mg/L | 1 mg/L | |
Taxifolin (1) | - | - | - | 37 ± 1% |
6-Bromotaxifolin (7) | - | - | - | 46 ± 4% |
6,8-Dibromotaxifolin (8) | - | - | - | 54 ± 5% |
Quercetin (2) | - | - | - | - |
8-Bromoquercetin (9) | - | - | - | - |
6,8-Dibromoquercetin (10) | - | - | - | - |
Silybin A (3a) | - | - | - | - |
6-Bromosilybin A (11) | - | - | - | 37 ± 1% |
8-Bromosilybin A (19) | - | - | - | 41 ± 3% |
6,8-Dibromosilybin A (12) | - | - | - | 40 ± 1% |
6,8,21-Tribromosilybin A (21) | - | - | - | reversion of resistance |
Silybin B (3b) | - | - | - | - |
6-Bromosilybin B (13) | - | - | - | 67 ± 4% |
6-Chlorosilybin B (28) | - | - | - | 34 ± 2% |
8-Bromosilybin B (20) | - | - | - | 48 ± 9% |
6,8-Dibromosilybin B (14) | - | - | - | 41 ± 1% |
6,8,21-Tribromosilybin B (22) | - | - | - | reversion of resistance |
2,3-Dehydrosilybin AB (4) | - | - | - | reversion of resistance [5 µM] |
8-Bromo-2,3-dehydrosilybin AB (16) | - | reversion of resistance | - | - |
6,8-Dibromo-2,3-dehydrosilybin AB (17) | - | 47 ± 3% | - | - |
Silychristin A (5) | - | - | - | - |
6,8-Dibromosilychristin A (15) | - | - | - | viability 63 ± 3% |
2,3-Dehydrosilychristin A (6) | - | - | 69 ± 4% [10 µM] | - |
8-Bromo-2,3-dehydrosilychristin A (18) | - | - | - | - |
Sulbactam (PC) | - | - | reversion of resistance | - |
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Hurtová, M.; Káňová, K.; Dobiasová, S.; Holasová, K.; Čáková, D.; Hoang, L.; Biedermann, D.; Kuzma, M.; Cvačka, J.; Křen, V.; et al. Selectively Halogenated Flavonolignans—Preparation and Antibacterial Activity. Int. J. Mol. Sci. 2022, 23, 15121. https://doi.org/10.3390/ijms232315121
Hurtová M, Káňová K, Dobiasová S, Holasová K, Čáková D, Hoang L, Biedermann D, Kuzma M, Cvačka J, Křen V, et al. Selectively Halogenated Flavonolignans—Preparation and Antibacterial Activity. International Journal of Molecular Sciences. 2022; 23(23):15121. https://doi.org/10.3390/ijms232315121
Chicago/Turabian StyleHurtová, Martina, Kristýna Káňová, Simona Dobiasová, Kateřina Holasová, Denisa Čáková, Lan Hoang, David Biedermann, Marek Kuzma, Josef Cvačka, Vladimír Křen, and et al. 2022. "Selectively Halogenated Flavonolignans—Preparation and Antibacterial Activity" International Journal of Molecular Sciences 23, no. 23: 15121. https://doi.org/10.3390/ijms232315121
APA StyleHurtová, M., Káňová, K., Dobiasová, S., Holasová, K., Čáková, D., Hoang, L., Biedermann, D., Kuzma, M., Cvačka, J., Křen, V., Viktorová, J., & Valentová, K. (2022). Selectively Halogenated Flavonolignans—Preparation and Antibacterial Activity. International Journal of Molecular Sciences, 23(23), 15121. https://doi.org/10.3390/ijms232315121