Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Activity
2.3. Molecular Docking Study
3. Materials and Methods
3.1. Instruments
3.2. Molecular Docking Details
3.3. Synthesis Methyl 2-(1H-indol-2-yl)acetate
3.4. General Procedure Indole Based 2,5-Disubstituted-1,3,4-Oxadiazoles (1–22)
3.4.1. 2-((1H-indol-2-yl) methyl)-5-(p-tolyl)-1,3,4-oxadiazole
3.4.2. 2-((1H-indol-2-yl) methyl)-5-(o-tolyl)-1,3,4-oxadiazole
3.4.3. 2-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) phenol
3.4.4. 3-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) phenol
3.4.5. 2-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) benzene-1,4-diol
3.4.6. 3-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) benzene-1,2-diol
3.4.7. 4-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) benzene-1,2-diol
3.4.8. 4-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) benzene-1,3-diol
3.4.9. 4-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl) phenol
3.4.10. 2-((1H-indol-2-yl) methyl)-5-(2-nitrophenyl)-1,3,4-oxadiazole
3.4.11. 2-((1H-indol-2-yl) methyl)-5-(3-nitrophenyl)-1,3,4-oxadiazole
3.4.12. 2-((1H-indol-2-yl) methyl)-5-(4-nitrophenyl)-1,3,4-oxadiazole
3.4.13. 2-(5-((1H-indol-2-yl) methyl)-1,3,4-oxadiazol-2-yl)-4-methoxyphenol
3.4.14. 2-((1H-indol-2-yl) methyl)-5-(3-bromo-4-fluorophenyl)-1,3,4-oxadiazole
3.4.15. 2-((1H-indol-2-yl) methyl)-5-(3-chlorophenyl)-1,3,4-oxadiazole
3.4.16. 2-((1H-indol-2-yl) methyl)-5-(pyridin-3-yl)-1,3,4-oxadiazole
3.4.17. 2-((1H-indol-2-yl) methyl)-5-(pyridin-4-yl)-1,3,4-oxadiazole
3.4.18. 2-((1H-indol-2-yl) methyl)-5-(2-fluorophenyl)-1,3,4-oxadiazole
3.4.19. 2-((1H-indol-2-yl) methyl)-5-(3-fluorophenyl)-1,3,4-oxadiazole
3.4.20. 2-((1H-indol-2-yl) methyl)-5-(4-fluorophenyl)-1,3,4-oxadiazole
3.4.21. 2-((1H-indol-2-yl) methyl)-5-(2-chlorophenyl)-1,3,4-oxadiazole
3.4.22. 2-((1H-indol-2-yl) methyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole
3.5. β-Glucuronidase Assay
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
S. No. | Yield (%) | IC50 (μM ± SEM a) | S. No. | Yield (%) | IC50 (μM ± SEM a) | ||
---|---|---|---|---|---|---|---|
1 | 36.4 ± 0.6 | 12 | 90 | 37.3 ± 0.7 | |||
2 | 26.2 ± 0.8 | 13 | 82 | 20.6 ± 0.5 | |||
3 | 6.2 ± 0.2 | 14 | 84 | NA b | |||
4 | 84 | 17.90 ± 0.4 | 15 | 83 | 34.6 ± 0.7 | ||
5 | 85 | 11.4 ± 0.30 | 16 | 85 | 46.4 ± 0.9 | ||
6 | 86 | 0.9 ± 0.01 | 17 | 87 | 43.1 ± 0.8 | ||
7 | 81 | 1.2 ± 0.01 | 18 | 88 | 5.0 ± 0.1 | ||
8 | 83 | 7.2 ± 0.10 | 19 | 90 | 10.5 ± 0.2 | ||
9 | 88 | 11.0 ± 0.4 | 20 | 92 | 17.0 ± 0.4 | ||
10 | 90 | 40.0 ± 0.7 | 21 | 90 | 6.0 ± 0.2 | ||
11 | 87 | NA b | 22 | 82 | 22.2 ± 0.5 | ||
d-saccharic acid 1,4 lactone c | 48.1 ± 1.2 |
Indole Based Oxadiazole Derivatives | Free Binding Energy (kcal/mol) | H-Bonds | Number of Closest Residues to the Docked Ligand in the Active Site | IC50 ± SEM |
---|---|---|---|---|
1 | −8.74 | 1 | 5 | 36.4 ± 0.6 |
3 | −8.17 | 1 | 4 | 6.2 ± 0.2 |
4 | −8.53 | 2 | 6 | 17.9 ± 0.4 |
5 | −9.16 | 3 | 7 | 11.4 ± 0.3 |
6 | −8.77 | 4 | 7 | 0.9 ± 0.01 |
7 | −8.88 | 4 | 9 | 1.2 ± 0.01 |
8 | −8.56 | 4 | 7 | 7.2 ± 0.10 |
9 | −8.65 | 3 | 7 | 11.04 ± 0.4 |
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Anouar, E.H.; Moustapha, M.E.; Taha, M.; Geesi, M.H.; Farag, Z.R.; Rahim, F.; Almandil, N.B.; Farooq, R.K.; Nawaz, M.; Mosaddik, A. Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives. Molecules 2019, 24, 963. https://doi.org/10.3390/molecules24050963
Anouar EH, Moustapha ME, Taha M, Geesi MH, Farag ZR, Rahim F, Almandil NB, Farooq RK, Nawaz M, Mosaddik A. Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives. Molecules. 2019; 24(5):963. https://doi.org/10.3390/molecules24050963
Chicago/Turabian StyleAnouar, El Hassane, Moustapha Eid Moustapha, Muhammad Taha, Mohammed H. Geesi, Zeinab R. Farag, Fazal Rahim, Noor Barak Almandil, Rai Khalid Farooq, Muhammad Nawaz, and Ashik Mosaddik. 2019. "Synthesis, Molecular Docking and β-Glucuronidase Inhibitory Potential of Indole Base Oxadiazole Derivatives" Molecules 24, no. 5: 963. https://doi.org/10.3390/molecules24050963