Synthesis, Molecular Docking and In Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine–Pyrazole Hybrid Derivatives
Abstract
1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. In Silico Molecular Docking Screenings
2.3. Pharmacological Screening
2.3.1. Anti-Microbial Activity
2.3.2. Anti-Oxidant Activity Using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) Scavenging
2.3.3. Examination of the Structural Activity Relationship (SAR)
3. Materials and Methods
3.1. General Information
3.2. Chemistry
3.2.1. 5-(3,4-Dimethylphenyl)-7-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carbonitrile (2)
3.2.2. 5-(3,4-Dimethylphenyl)-3-methyl-7-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carbonitrile (3)
3.2.3. 5-(3,4-Dimethylphenyl)-3-phenyl-7-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carbonitrile (4)
3.2.4. 5-(3,4-Dimethylphenyl)-7-(thiophen-2-yl)-3-thioxo-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridine-8-carbonitrile (5)
3.2.5. 5-(3,4-Dimethylphenyl)-7-(thiophen-2-yl)tetrazolo[1,5-a]pyridine-8-carbonitrile (6)
3.2.6. 6-(3,4-Dimethylphenyl)-3,4-dioxo-8-(thiophen-2-yl)-3,4-dihydro-2H-pyrido[2,1-c][1,2,4] triazine-9-carbonitrile (7)
3.2.7. 6-(3,4-Dimethylphenyl)-3-oxo-8-(thiophen-2-yl)-3,4-dihydro-2H-pyrido[2,1-c][1,2,4]triazine-9-carbonitrile (8)
3.2.8. 6-(3,4-Dimethylphenyl)-4-oxo-8-(thiophen-2-yl)-3,4-dihydro-2H-pyrido[2,1-c][1,2,4]triazine-9-carbonitrile (9)
3.2.9. 6-(3,4-Dimethylphenyl)-8-(thiophen-2-yl)-3,4-dihydro-2H-pyrido[2,1-c][1,2,4]triazine-9-carbonitrile (10)
3.2.10. 2-(3,5-Dimethyl-1H-pyrazol-1-yl)-6-(3,4-dimethylphenyl)-4-(thiophen-2-yl)nicotinonitrile (11)
3.2.11. 6-(3,4-Dimethylphenyl)-2-(3,5-dioxopyrazolidin-1-yl)-4-(thiophen-2-yl)nicotinonitrile (12)
3.2.12. 2-(5-Amino-3-oxo-2,3-dihydropyrazol-1-yl)-6-(3,4-dimethylphenyl)-4-(thiophen-2-yl)nicotinonitrile (13)
3.2.13. 6-(3,4-Dimethylphenyl)-2-(5-oxo-3-phenyl-4,5-dihydropyrazol-1-yl)-4-(thiophen-2-yl)nicotinonitrile (14)
3.2.14. 6-(3,4-Dimethylphenyl)-2-(3-methyl-5-oxo-4,5-dihydropyrazol-1-yl)-4-(thiophen-2-yl)nicotinonitrile (15)
3.3. In Silico Molecular Docking Screenings
3.4. In Vitro Anti-Microbial Screenings
3.5. DPPH Radical Scavenging Activity
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Compound Code | Minimum Binding Energy (kJ/mol) | Estimated Inhibition Constant, Ki = uM (micromol) |
---|---|---|
1 | −6.08 | 35 uM |
2 | −7.19 | 5.39 uM |
3 | −7.34 | 4.16 uM |
4 | −7.55 | 2.94 uM |
5 | −6.28 | 25.04 uM |
6 | −7.51 | 3.13 uM |
7 | −7.77 | 2.00 uM |
8 | −7.84 | 1.79 uM |
9 | −7.29 | 4.51 uM |
10 | −7.62 | 2.59 uM |
11 | −6.55 | 15.69 uM |
12 | −6.15 | 30.87 uM |
13 | −6.29 | 24.67 uM |
14 | −7.03 | 7.00 uM |
15 | −6.10 | 33.94 uM |
Sample Code Tested Microorganisms | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | Control |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
FUNGI | Ketoconazole | |||||||||||||||
Aspergillus flavus (RCMB 002002) | NA | NA | NA | 7 | 12 | 8 | 9 | 11 | NA | 11 | 10 | 7 | 8 | 7 | NA | 16 |
Candida albicans RCMB 005003 (1) ATCC 10231 | 9 | NA | NA | NA | 12 | 11 | 10 | 12 | 13 | 15 | 17 | 10 | 9 | 10 | 9 | 20 |
Gram Positive Bacteria: | Gentamycin | |||||||||||||||
Staphylococcus aureus (RCMB010010) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 10 | NA | 11 | 8 | 24 |
Bacillus subtilis RCMB 015 (1) NRRL B-543 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 26 |
Gram Negatvie Bacteria: | Gentamycin | |||||||||||||||
Escherichia coli (RCMB 010052) ATCC 25955 | 12 | 13 | 18 | NA | 8 | NA | 10 | 12 | NA | 13 | 9 | NA | NA | 11 | 12 | 30 |
Salmonella typhimurium RCMB 006 (1) ATCC 14028 | NA | NA | NA | NA | 15 | NA | NA | NA | NA | 7 | 8 | 10 | NA | NA | NA | 17 |
Compound Code | IC50 (μg/mL) |
---|---|
Tocopherol | 6.78 |
1 | 22.8 |
2 | >1000 |
3 | 252.7 |
4 | >1000 |
5 | 110.3 |
6 | 70.5 |
7 | 700 |
8 | - |
9 | 602.5 |
10 | - |
11 | 508.5 |
12 | 242.7 |
13 | 218.5 |
14 | 3.49 |
15 | 4.7 |
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Flefel, E.M.; El-Sofany, W.I.; El-Shahat, M.; Naqvi, A.; Assirey, E. Synthesis, Molecular Docking and In Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine–Pyrazole Hybrid Derivatives. Molecules 2018, 23, 2548. https://doi.org/10.3390/molecules23102548
Flefel EM, El-Sofany WI, El-Shahat M, Naqvi A, Assirey E. Synthesis, Molecular Docking and In Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine–Pyrazole Hybrid Derivatives. Molecules. 2018; 23(10):2548. https://doi.org/10.3390/molecules23102548
Chicago/Turabian StyleFlefel, Eman M., Walaa I. El-Sofany, Mahmoud El-Shahat, Arshi Naqvi, and Eman Assirey. 2018. "Synthesis, Molecular Docking and In Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine–Pyrazole Hybrid Derivatives" Molecules 23, no. 10: 2548. https://doi.org/10.3390/molecules23102548
APA StyleFlefel, E. M., El-Sofany, W. I., El-Shahat, M., Naqvi, A., & Assirey, E. (2018). Synthesis, Molecular Docking and In Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine–Pyrazole Hybrid Derivatives. Molecules, 23(10), 2548. https://doi.org/10.3390/molecules23102548