Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry—Design and Synthesis
2.2. Structural Analysis
2.3. Biological Screening
2.3.1. In Vitro Antimicrobial Activity
2.3.2. In Vitro Cell Viability
2.4. Similarity-Mediated Property Mapping
3. Materials and Methods
3.1. Chemisty
3.1.1. Synthesis of Acetanilide Derivatives 2a–l
3.1.2. Synthesis of Aniline Derivatives 3a–l
3.1.3. Synthesis of 5-Methyl-12H-Quino[3,4-b][1,4]Benzothiazine Chloride 6a–l
3.2. X-ray Structural Analysis
3.3. Thin-Layer Chromatography
3.4. Biological Evaluation
3.4.1. In Vitro Antibacterial Evaluation
3.4.2. Determination of Minimum Bactericidal Concentrations
3.4.3. MTT Assay
3.4.4. In Vitro Antimycobacterial Evaluation
3.4.5. In Vitro Cell Viability Analysis
3.5. Principal Component and Hierarchical Clustering Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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No. | MIC [μM] MBC [μM] | IC50 [µM] NHDF | logPTLC | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
SA | MRSA1 | MRSA2 | MRSA3 | EF | VRE1 | VRE2 | VRE3 | MS | MM | |||
6a | 22.3 22.3 | 22.3 22.3 | 22.3 22.3 | 11.1 11.1 | 89.1 89.1 | 89.1 89.1 | 89.1 89.1 | 89.1 178 | 22.3 – | 22.3 – | >100 | 1.65 |
6b | 22.3 44.6 | 44.6 44.6 | 44.6 44.6 | 22.3 22.3 | 89.1 89.1 | 178 178 | 178 178 | 89.1 89.1 | 22.3 – | 22.3 – | 65.5 | 1.99 |
6c | 178 178 | 178 178 | 178 178 | 178 178 | 178 178 | 178 178 | 178 178 | 89.1 178 | 44.6 – | 44.6 – | >100 | 1.18 |
6d | 44.8 44.8 | 44.8 44.8 | 89.6 89.6 | 44.8 44.8 | 44.8 44.8 | 44.8 44.8 | 44.8 44.8 | 22.4 44.8 | 22.4 – | 11.2 – | >100 | 2.98 |
6e | 44.8 44.8 | 44.8 44.8 | 44.8 44.8 | 22.4 22.4 | 89.6 89.6 | 179 179 | 179 179 | 89.6 89.6 | 22.4 – | 11.2 – | >100 | 2.47 |
6f | 359 359 | 359 359 | 359 359 | 179 359 | 179 359 | 359 359 | 359 359 | 179 179 | 89.6 – | 44.8 – | >100 | 2.29 |
6g | 45.1 45.1 | 45.1 45.1 | 45.1 45.1 | 45.1 45.1 | 90.1 90.1 | 90.1 90.1 | 90.1 90.1 | 90.1 90.1 | 22.5 – | 11.3 – | >100 | 2.11 |
6h | 45.1 45.1 | 90.1 90.1 | 90.1 90.1 | 45.1 45.1 | 45.1 45.1 | 45.1 45.1 | 45.1 45.1 | 22.5 22.5 | 22.5 – | 22.5 – | >100 | 1.74 |
6i | 180 180 | 180 361 | 361 361 | 180 180 | 361 361 | 180 180 | 180 180 | 180 180 | 90.1 – | 45.1 – | 47.5 | 2.20 |
6j | 9.83 9.83 | 4.91 9.83 | 9.83 9.83 | 2.46 2.46 | 19.7 39.3 | 19.7 19.7 | 78.6 78.6 | 39.3 39.3 | 9.83 – | 2.50 – | 37.7 | 3.41 |
6k | 19.7 19.7 | 19.7 19.7 | 9.83 19.7 | 9.83 9.83 | 78.6 78.6 | 78.6 78.6 | 157 157 | 157 157 | 19.7 – | 19.7 – | >100 | 3.48 |
6l | 39.3 39.3 | 39.3 78.6 | 78.6 78.6 | 39.3 39.3 | 157 157 | 157 157 | 157 157 | 157 157 | 39.3 – | 9.83 – | >100 | 3.10 |
AMP | 5.72 5.72 | – | – | – | 2.81 2.81 | 11.5 11.5 | 11.5 11.5 | 11.5 11.5 | – | – | – | – |
OXA | 1.25 1.25 | 79.8 79.8 | 29.7 29.7 | 9.9 9.9 | – | – | – | – | – | – | – | – |
TTC | 4.52 NT | 36.1 NT | 36.1 NT | >72.1 NT | – | – | – | – | – | – | – | – |
CPX | 1.51 NT | 48.3 NT | 24.2 NT | 24.2 NT | – | – | – | – | – | – | – | – |
INH | – | – | – | – | – | – | – | – | 117 – | 467 – | – | – |
RIF | – | – | – | – | – | – | – | – | 19.4 – | 2.43 – | – | – |
No. | Conc. | S. aureus Respiration Inhibition [%] |
---|---|---|
6a | 2× MIC (2× MBC) | 97.7 |
6e | 2× MIC (2× MBC) | 97.4 |
6g | 2× MIC (2× MBC) | 96.8 |
6j | 0.5× MIC (0.5× MBC) | 91.3 |
6k | 2× MIC (2× MBC) | 97.6 |
APM | 16× MIC (>16× MBC) | 81.9 |
CPX | 32× MIC (32× MBC) | 96.1 |
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Kisiel-Nawrot, E.; Pindjakova, D.; Latocha, M.; Bak, A.; Kozik, V.; Suwinska, K.; Sochanik, A.; Cizek, A.; Jampilek, J.; Zięba, A. Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives. Int. J. Mol. Sci. 2022, 23, 15078. https://doi.org/10.3390/ijms232315078
Kisiel-Nawrot E, Pindjakova D, Latocha M, Bak A, Kozik V, Suwinska K, Sochanik A, Cizek A, Jampilek J, Zięba A. Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives. International Journal of Molecular Sciences. 2022; 23(23):15078. https://doi.org/10.3390/ijms232315078
Chicago/Turabian StyleKisiel-Nawrot, Ewa, Dominika Pindjakova, Malgorzata Latocha, Andrzej Bak, Violetta Kozik, Kinga Suwinska, Aleksander Sochanik, Alois Cizek, Josef Jampilek, and Andrzej Zięba. 2022. "Design, Synthesis and Antimicrobial Properties of New Tetracyclic Quinobenzothiazine Derivatives" International Journal of Molecular Sciences 23, no. 23: 15078. https://doi.org/10.3390/ijms232315078