Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Urease Inhibitory Assay
2.3. In Silico Studies of Indole-3-Carbaldehyde Oxime Derivatives
2.4. Drug-Likeness of Indole-3-Carbaldehyde Oxime Derivatives
3. Materials and Methods
3.1. General
3.2. Synthesis of (Z)-N-Hydroxy-1-(1H-indole-3-yl)methanimine (2)
3.2.1. Methods a and b
3.2.2. Methods c and d
3.3. Synthesis of (E)-N-Hydroxy-1-(1H-indole-3-yl)methanimine (3)
3.4. Synthesis of 1-Methyl-1H-indole-3-carbaldehyde (4)
3.5. Synthesis of (Z/E)-N-Hydroxy-1-(1-methyl-1H-indol-3-yl)methanimine (6 and 7)
3.6. Synthesis of 1-Benzyl-1H-indole-3-carbaldehyde (5)
3.7. Synthesis of (Z/E)-1-(1-Benzyl-1H-indol-3-yl)-N-hydroxymethanimine (8 and 9)
3.8. Urease Inhibitory Assay
- = Absorbance of the control sample (C)
- = Absorbance of the negative control sample (N)
- = Absorbance of the test sample (T1 to T7)
- = Absorbance of the negative control of the test sample (N1 to N7)
3.9. Molecular Docking Studies
3.10. Drug-Likeness Prediction of Indole-3-Carbaldehyde Oxime Derivatives
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Compound | IC50 Value (mM) | Maximum Percentage of Inhibition |
---|---|---|
Thiourea | 0.2387 ± 0.0048 | 85.14 |
2 | 0.1412 ± 0.0075 | 67.81 |
6 | 0.1405 ± 0.0045 | 77.05 |
7 | 0.1530 ± 0.0016 | 57.17 |
8 | 0.0516 ± 0.0035 | 83.78 |
9 | 0.0345 ± 0.0008 | 86.09 |
Compound | ChemPLP Score |
---|---|
Thiourea | 23.27 |
2 | 60.50 |
6 | 62.06 |
7 | 64.92 |
8 | 80.47 |
9 | 82.17 |
Compound | MW a/(g/mol) | TPSA b (Å) | Consensus Log Po/w c | Log S d (mol/L) | n-HA e | n-HD f | n-Violations g | GI Absorption h |
---|---|---|---|---|---|---|---|---|
Thiourea | 76.12 | 84.13 | −0.43 | 0.29 | 2 | 4 | 0 | high |
2 | 160.17 | 48.38 | 1.72 | −2.49 | 3 | 2 | 0 | high |
6 | 174.20 | 37.52 | 1.71 | −2.78 | 3 | 1 | 0 | high |
7 | 174.20 | 37.52 | 1.74 | −2.78 | 3 | 1 | 0 | high |
8 | 250.30 | 37.52 | 2.99 | −4.65 | 3 | 1 | 0 | high |
9 | 250.30 | 37.52 | 3.01 | −4.65 | 3 | 1 | 0 | high |
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Kalatuwawege, I.P.; Gunaratna, M.J.; Udukala, D.N. Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori. Molecules 2021, 26, 6658. https://doi.org/10.3390/molecules26216658
Kalatuwawege IP, Gunaratna MJ, Udukala DN. Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori. Molecules. 2021; 26(21):6658. https://doi.org/10.3390/molecules26216658
Chicago/Turabian StyleKalatuwawege, Ishani P., Medha J. Gunaratna, and Dinusha N. Udukala. 2021. "Synthesis, In Silico Studies, and Evaluation of Syn and Anti Isomers of N-Substituted Indole-3-carbaldehyde Oxime Derivatives as Urease Inhibitors against Helicobacter pylori" Molecules 26, no. 21: 6658. https://doi.org/10.3390/molecules26216658