The Importance of Substituent Position for Antibacterial Activity in the Group of Thiosemicarbazide Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antibacterial Evaluation
2.3. Docking
3. Experiment
3.1. Chemistry
3.1.1. General Comments
3.1.2. Synthesis of Thiosemicarbazide Derivatives
- Yield 64%, m.p. 171–172 °C. Spectral data were as follows: IR (cm−1) KBr: 3320 (NH); 1669 (C=O), 1573 (CHarom); 1362 (C=S); 1263 (C-O-C). 1H NMR (DMSO-d6) δ (ppm): 3.75 (s, 3H, CH3), 6.75 (d, 1H, CHarom, J = 8.7 Hz), 7.05 (d, 1H, CHarom, J = 7.8 Hz), 7.18 (bs, 1H, CHarom,), 7.25 (t, 1H, CHarom, J = 8.1 Hz), 7.33 (d, 1H, CHarom, J = 7.9 Hz), 7.35–7.36 (m, 1H, CHarom), 7.59–7.62 (m, 1H, CHarom), 7.85 (bs, 1H, CHarom,), 9.84 (bs, 2H, 2NH), 10.33 (s, 1H, NH). 13C NMR (DMSO-d6) δ (ppm): 55.5; 110.90; 111.8; 116.7 (d, J = 22.0 Hz); 118.3; 122.2; 124.4; 129.3; 131.1; 133.7; 140.7; 159.5; 160.1 (d, J = 250.5 Hz); 163.9; 181.4. Elemental analysis for C15H14FN3O2S. Calculated: C 56.41; H 4.42; N 13.16. Found: C 56.43; H 4.40; N 13.15.
- Yield 93%, m.p. 172–173 °C. Spectral data were as follows: IR (cm−1) KBr: 3319 (NH); 1638 (C=O), 1581 (CHarom); 1361 (C=S); 1259 (C-O-C). 1H NMR (DMSO-d6) δ (ppm): 3.75 (s, 3H, CH3), 6.75 (d, 1H, CHarom, J = 7.2 Hz), 7.04 (d, 1H, CHarom, J = 8.0 Hz), 7.12 (bs, 1H, CHarom,), 7.24 (t, 1H, CHarom, J = 8.1 Hz), 7.46 (t, 1H, CHarom, J = 8.5 Hz), 7.59–7.62 (m, 1H, CHarom J = 7.7 Hz), 7.77 (d, 1H, CHarom J = 9.7 Hz), 7.80 (d, 1H, CHarom, J = 6.3 Hz), 9.77 (bs, 2H, 2NH), 10.65 (s, 1H, NH). 13C NMR (DMSO-d6) δ (ppm): 55.5; 111.0; 112.1; 115.2 (d, J = 24.0 Hz); 118.5; 119.2 (d, J = 20.8 Hz); 124.5; 129.1; 130.9; 135.3; 140.7; 159.4; 162.2 (d, J = 243.0 Hz), 165.2; 181.3. Elemental analysis for C15H14FN3O2S. Calculated: C 56.41; H 4.42; N 13.16. Found: C 56.42; H 4.39; N 13.13.
- Yield 87% (0.24 g), m.p. 173–175 °C. Spectral data were as follows: IR (cm−1) KBr: 3323 (NH); 1670 (C=O), 1573 (CHarom); 1365 (C=S); 1264 (C-O-C).1H NMR (DMSO-d6) δ ppm: 3.75 (s, 3H, CH3), 6.76 (d, 1H, CHarom, J = 8.3 Hz), 7.03 (d, 1H, CHarom, J = 8.0 Hz), 7.11 (bs, 1H, CHarom,), 7.25 (t, 1H, CHarom, J = 8.1 Hz), 7.78 (t, 1H, CHarom, J = 7.8 Hz), 7.98 (d, 1H, CHarom J = 7.8 Hz), 8.24 (d, 1H, CHarom J = 7.8 Hz), 8.30 (s, 1H, CHarom), 9.80 (s, 2H, 2NH), 10.82 (s, 1H, NH). 13C NMR (DMSO-d6) δ (ppm): 55.5; 111.0; 112.2; 118.6; 121.7; 125.1 (d, J = 49.4 Hz); 127.1; 128.8; 129.54 (q, J = 31.5 Hz); 130.1; 132.4; 134.0; 140.7; 159.4; 165.1, 181.4. Elemental analysis for C16H14F3N3O2S. Calculated: C 52.03; H 3.82; N 11.38. Found: C 52.00; H 3.79; N 11.36.
3.2. Microbiology
3.3. Docking
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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MIC—Minimal Inhibitory Concentration [µg/mL] | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Microorganism | T1A | T2A | T3A | T4A | T5A | T6A | T7A | T8A | T9A | CIP | |
Gram-positive bacteria | S. aureus NCTC 4163 | >256 | >256 | 64 | 32 | 128 | 256 | 64 | 64 | 64 | 0.125 |
S. aureus ATCC 25923 | >256 | >256 | 64 | 32 | 128 | 256 | 64 | 64 | 64 | 0.25 | |
S. aureus ATCC 6538 | >256 | >256 | 64 | 64 | 128 | 256 | 64 | 128 | 64 | 0.125 | |
S. aureus ATCC 29213 | >256 | >256 | 128 | 64 | 128 | 256 | 128 | 128 | 64 | 0.5 | |
S. epidermidis ATCC 12228 | >256 | >256 | >256 | 128 | 256 | 256 | >256 | 256 | 64 | 0.25 | |
S. epidermidis ATCC 35984 | >256 | >256 | >256 | 256 | 256 | 256 | >256 | 256 | 128 | 0.125 | |
Gram-negative bacteria | E. coli ATCC 25922 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | 0.008 |
P. aeruginosa ATCC 15442 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | >256 | 0.125 |
Compounds | S. aureus ATCC 25923 | S. epidermidis ATCC 12228 |
MIC [µg/mL] | MIC [µg/mL] | |
T1A | >256 | >256 |
T1B | 62.5 | 62.5 |
T2A | >256 | >256 |
T2B | 1000 | 500 |
T3A | 64 | >256 |
T3B | 1000 | 125 |
T4A | 32 | 256 |
T4B | 1000 | 1000 |
T5A | 128 | 256 |
T5B | 125 | >1000 |
T6A | 256 | 256 |
T6B | 500 | 250 |
T7A | 64 | >256 |
T7B | 250 | 62.5 |
T8A | 64 | 256 |
T8B | 250 | 31.25 |
T9A | 64 | 128 |
T9B | 500 | 125 |
Compounds | Topoisomerase IV (3LTN) | DNA Gyrase (6FQM) | Ddl (1IOV) | |||
---|---|---|---|---|---|---|
Binding Energy Kcal/mol | Inhibition Constant, Ki uM | Binding Energy Kcal/mol | Inhibition Constant, Ki uM | Binding Energy Kcal/mol | Inhibition Constant, Ki uM | |
T1A | −8.32 | 0.79 | −7.84 | 1.79 | −8.73 | 0.39 |
T2A | −7.86 | 1.85 | −8.73 | 0.39 | −7.83 | 1.83 |
T3A | −8.03 | 1.3 | −9.92 | 0.053 | −8.64 | 0.46 |
T4A | −8.55 | 0.15 | −9.78 | 0.068 | −8.99 | 0.26 |
T5A | −6.59 | 14.87 | −6.64 | 13.50 | −8.88 | 0.31 |
T6A | −7.36 | 4.03 | −8.48 | 0.20 | −8.19 | 0.99 |
T7A | −6.64 | 13.50 | −8.67 | 0.45 | −9.03 | 0.24 |
T8A | −7.83 | 1.82 | −9.85 | 0.60 | −8.78 | 0.35 |
T9A | −8.48 | 0.19 | −9.50 | 0.11 | −9.55 | 0.10 |
PD 0305970 | −8.38 | 0.72 | - | - | - | - |
E32 | - | - | −9.29 | 0.155 | - | - |
POV | - | - | - | - | −9.50 | 0.11 |
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Janowska, S.; Stefańska, J.; Khylyuk, D.; Wujec, M. The Importance of Substituent Position for Antibacterial Activity in the Group of Thiosemicarbazide Derivatives. Molecules 2024, 29, 1333. https://doi.org/10.3390/molecules29061333
Janowska S, Stefańska J, Khylyuk D, Wujec M. The Importance of Substituent Position for Antibacterial Activity in the Group of Thiosemicarbazide Derivatives. Molecules. 2024; 29(6):1333. https://doi.org/10.3390/molecules29061333
Chicago/Turabian StyleJanowska, Sara, Joanna Stefańska, Dmytro Khylyuk, and Monika Wujec. 2024. "The Importance of Substituent Position for Antibacterial Activity in the Group of Thiosemicarbazide Derivatives" Molecules 29, no. 6: 1333. https://doi.org/10.3390/molecules29061333