Microwave Optimized Synthesis of N-(adamantan-1-yl)-4-[(adamantan-1-yl)-sulfamoyl]benzamide and Its Derivatives for Anti-Dengue Virus Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. In-Vitro Anti-DENV2 Activity and Cytotoxicity Evaluations
2.3. Molecular Modelling
3. Materials and Methods
3.1. Chemistry
3.1.1. General Information
3.1.2. Synthesis of N-(adamantan-1-yl)-4-[(adamantan-1-yl)sulfamoyl]benzamide (3)
3.1.3. Synthesis of N-(adamantan-1-yl)benzamide (6)
3.1.4. Synthesis of N-(adamantan-1-yl)-4-sulfamoylbenzamide (7)
3.2. Anti-DENV2 Activity Assay
3.2.1. Cells and Viruses
3.2.2. Cell-Based Flavivirus Immunodetection (CFI) Assay
3.3. Cytotoxicity Assay
3.4. Molecular Modelling
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of compounds 3, 6 and 7 are available from the authors upon request. |
Compound | Time | % Yields | ||
---|---|---|---|---|
Conventional | MWAM | Conventional | MWAM | |
3 | 48 h 1 | 30 min 2 | 25 3 | 78 3 |
6 | 2 h | 10 min | 25 4 | 64 4 |
7 | 2 h | 10 min | 40 4 | 82 4 |
Compound | DENV2 IC50 a | CC50 b |
---|---|---|
1 | >100 | >100 |
3 | 22.4 ± 7.7 | >100 |
6 | >100 | >100 |
7 | 42.8 ± 8.6 | >100 |
Compound | Binding Affinity | Residues Interacting with Ligand |
---|---|---|
SF1 | −7.835 | His51, Tyr151 |
SF2 | −8.011 | His51, Leu128 |
1 | −4.234 | None |
3 | −7.413 | His51, Gly153 |
6 | −6.124 | None |
7 | −7.123 | Val72, Asp75, Gly153 |
Bz-Nle-Lys-Arg-Arg-H | −11.323 | His51, Val72, Asp75, Asn152 |
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Joubert, J.; Foxen, E.B.; Malan, S.F. Microwave Optimized Synthesis of N-(adamantan-1-yl)-4-[(adamantan-1-yl)-sulfamoyl]benzamide and Its Derivatives for Anti-Dengue Virus Activity. Molecules 2018, 23, 1678. https://doi.org/10.3390/molecules23071678
Joubert J, Foxen EB, Malan SF. Microwave Optimized Synthesis of N-(adamantan-1-yl)-4-[(adamantan-1-yl)-sulfamoyl]benzamide and Its Derivatives for Anti-Dengue Virus Activity. Molecules. 2018; 23(7):1678. https://doi.org/10.3390/molecules23071678
Chicago/Turabian StyleJoubert, Jacques, Eugene B. Foxen, and Sarel F. Malan. 2018. "Microwave Optimized Synthesis of N-(adamantan-1-yl)-4-[(adamantan-1-yl)-sulfamoyl]benzamide and Its Derivatives for Anti-Dengue Virus Activity" Molecules 23, no. 7: 1678. https://doi.org/10.3390/molecules23071678