Chemical Synthesis and Hemi-Synthesis of Novel Benzimidazole Derivatives Using Microwave-Assisted Process: Chemical Characterization, Bioactivities and Molecular Docking †
Abstract
:1. Introduction
- A chemical synthesis and hemi-synthesis of new benzimidazole derivatives;
- A physicochemical characterization (purification and structural analysis) of the synthesized compounds by 1H NMR spectroscopy and FTIR;
- Evaluation of antioxidant and antimicrobial activities by in-vitro assays;
- Evaluation of docking scores of the synthesized compounds on 4QGH (PDB: Protein data base entry) protein of Staphylococcus aureus thymidylate kinase (TMK).
2. Methods
2.1. Plant Material and Extraction Procedure
2.2. Essential Oil Analysis
2.3. Synthesis Procedure
2.3.1. Synthesis/Hemi-Synthesis of Three Benzimidazole Aldehyde Derivatives
2.3.2. Synthesis of Benzimidazole Phenolic Acid Derivatives
2.4. Fractionating/Purification
2.5. Structural Analysis
2.6. Bioactivities Properties Evaluation
2.6.1. Antioxidant Activity
2.6.2. Antimicrobial Activity
2.7. Molecular Docking Study
3. Results and Discussion
3.1. GC/MS Profiles of Essential Oils of Cinnamon and Lemongrass
3.2. Separation and Purification of Synthetic Products
3.3. Structural Analysis
3.4. Bioactivity Properties
3.4.1. Antioxidant Activity
3.4.2. Antimicrobial Activity
3.5. Molecular Docking Results
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A
Rt (min) | Concentration % | Compound |
---|---|---|
4.3 | 0.02 | Tetrachloroethylene |
8.6 | 0.04 | γ-Terpinene |
9.4 | 0.03 | Camphene |
10.6 | 0.25 | Benzaldehyde |
14.6 | 0.05 | D-Limonene |
23.1 | 0.05 | 1,2-Chromene |
24.6 | 0.92 | Hydrocinnamaldehyde |
25.3 | 0.07 | Phenyl 2-Propynyl Ether |
34.9 | 90.54 | Cinnamaldehyde |
38.2 | 0.61 | α-Cubebene |
39.1 | 0.06 | Oxirane |
39.4 | 0.05 | α-Copaene |
39.8 | 0.07 | (+)-Sativene |
40.7 | 0.04 | (−)-Isosativene |
41.3 | 0.05 | β-Thujene |
43.2 | 0.03 | Benzenamine |
43.8 | 2.87 | Coumarin |
45.0 | 0.21 | Naphthalene |
46.1 | 0.05 | Amide Hydrocinnamique |
46.5 | 0.66 | α-Cadinene |
47.9 | 0.90 | δ-Cadinene |
48.5 | 0.19 | 1H-3a,7-Methanoazulene |
49.2 | 1.13 | 4-Methoxycinnamaldehyde |
53.4 | 0.08 | 2,4-Hexadiene |
55.9 | 0.36 | γ-Cadinene |
Rt (Min) | % | Compound |
---|---|---|
4.6 | 0.02 | Tridodecylamine |
7.8 | 0.08 | D-Limonene |
12.2 | 4.55 | β-Myrcene |
14.6 | 0.1 | α-Limonene |
15.4 | 0.31 | α-Pinene |
16.1 | 0.33 | β-Ocimene |
16.4 | 0.06 | Myrcenylacetat |
19.3 | 0.05 | Nortricyclene |
19.8 | 0.4 | Furan |
20.3 | 1.52 | L-Linalool |
21.3 | 0.06 | Fenchol |
22.5 | 0.23 | Cyclohexene |
23.3 | 0.44 | Trans-Chrysanthemal |
23.6 | 0.35 | (R)-(+)-Citronellal |
24.5 | 0.81 | Cyclopropene |
25.8 | 1.29 | 7-Methyl-1-Nonyne |
28.4 | 0.11 | O-Mentha-1(7),8-Dien-3-Ol |
30.5 | 34.87 | Neral |
32.8 | 43.88 | Cis-Citral |
33.7 | 0.32 | Geranial |
34.2 | 0.22 | Geranyl Vinyl Ether |
35.8 | 3.5 | Geraniol |
38.4 | 0.24 | Nerol |
39.5 | 3.37 | Nerol Acetate |
40.2 | 0.65 | Geranic Acid |
41.3 | 0.21 | β-Caryophyllene |
42.4 | 0.17 | α-Bergamotene |
50.1 | 0.06 | Neryl Acetate |
51.4 | 0.08 | β-Citronellal |
54.1 | 0.14 | Trans-β-Farnesene |
70.8 | 0.18 | Farnesyl |
72.5 | 0.06 | Trans-Caryophyllene |
75.3 | 0.11 | Cyclopropane Carboxamide |
76.7 | 0.2 | α-Trans-Sequicyclogeraniol |
78.3 | 0.31 | Farnesol |
79.6 | 0.14 | 3,7-Nonadien-2-Ol |
80.0 | 0.07 | Geranylacetone |
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Synthetized Molecule | Antioxidant Activity EC5O (µg/mL) | |||
---|---|---|---|---|
DPPH Test | Ferric Ion Reducing Power | β-Carotene | TBARS | |
1b | 53 ± 1 | 54 ± 4 | 192 ± 7 | 134 ± 2 |
2b | 139 ± 4 | 101 ± 7 | 181 ± 5 | 156 ± 52 |
3b | 220 ± 15 | 102 ± 22 | 220 ± 11 | 134 ± 2 |
4b | 767 ± 6 | 544 ± 4 | 872 ± 37 | 1554 ± 25 |
5b | 78 ± 5 | 96 ± 8 | 94 ± 3 | 101 ± 7 |
BHT | 23 ± 3 | 30 ± 6 | 48 ± 5 | 76 ± 1 |
Trolox | 51 ± 4 | 44 ± 4 | 63 ± 2 | 84 ± 6 |
Synthetized Molecule | E. coli | S. aureus | P. aeruginosa | S. typhi | C. albicans | |||||
---|---|---|---|---|---|---|---|---|---|---|
MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | |
1b | 0.3125 | 2.5 | ˂0.3125 | 1.25 | 0.625 | 5 | 0.3125 | 5 | ˂0.3125 | 2.5 |
2b | 0.3125 | 10 | 0.3125 | 5 | 1.25 | >10 | 0.3125 | 5 | 0.625 | 2.5 |
3b | 0.3125 | 5 | 0.3125 | 2.5 | 2.5 | 5 | 0.3125 | 5 | 0.3125 | 5 |
4b | 2.5 | 2.5 | 1.25 | 1.25 | >10 | >10 | 2.5 | >10 | 5 | >10 |
5b | 0.625 | 2.5 | 0.156 | 0.625 | 2.5 | 5 | 0.3125 | 5 | 0.3125 | 5 |
Antibiotics | ||||||||||
Gentamicine 10Ug | ˂0.078 | ˂0.078 | 0.156 | ˂0.156 | nt | |||||
Ceftazidime 30Ug | ˂0.156 | 0.156 | 0.156 | ˂0.156 | nt | |||||
Nystatine | nt | nt | nt | nt | ˂0.078 |
Protein | Interacting Residue | Binding Energy, ΔG (Kcal/Mol) | Inhibition Constant, Ki (µm) |
---|---|---|---|
thymidylate kinase TMK (4QGH) | 1b | −8.3 | 0.812 |
5b | −9.4 | 0.127 |
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Sameut, A.; Zanndouche, S.Y.; Boumaza, C.; Dikes, C.; Ziani, B.E.C. Chemical Synthesis and Hemi-Synthesis of Novel Benzimidazole Derivatives Using Microwave-Assisted Process: Chemical Characterization, Bioactivities and Molecular Docking. Chem. Proc. 2021, 3, 71. https://doi.org/10.3390/ecsoc-24-08306
Sameut A, Zanndouche SY, Boumaza C, Dikes C, Ziani BEC. Chemical Synthesis and Hemi-Synthesis of Novel Benzimidazole Derivatives Using Microwave-Assisted Process: Chemical Characterization, Bioactivities and Molecular Docking. Chemistry Proceedings. 2021; 3(1):71. https://doi.org/10.3390/ecsoc-24-08306
Chicago/Turabian StyleSameut, Asmaâ, Sarah Yasmine Zanndouche, Chaimaa Boumaza, Chaima Dikes, and Borhane Eddine Cherif Ziani. 2021. "Chemical Synthesis and Hemi-Synthesis of Novel Benzimidazole Derivatives Using Microwave-Assisted Process: Chemical Characterization, Bioactivities and Molecular Docking" Chemistry Proceedings 3, no. 1: 71. https://doi.org/10.3390/ecsoc-24-08306
APA StyleSameut, A., Zanndouche, S. Y., Boumaza, C., Dikes, C., & Ziani, B. E. C. (2021). Chemical Synthesis and Hemi-Synthesis of Novel Benzimidazole Derivatives Using Microwave-Assisted Process: Chemical Characterization, Bioactivities and Molecular Docking. Chemistry Proceedings, 3(1), 71. https://doi.org/10.3390/ecsoc-24-08306