New Nitrogen Compounds Coupled to Phenolic Units with Antioxidant and Antifungal Activities: Synthesis and Structure–Activity Relationship
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Antioxidant Capacity
2.3. Antifungal Activity
3. Materials and Methods
3.1. Chemistry
3.1.1. General Procedure for the Synthesis of the 1-amino-2-arylidenamine-1,2-(dicyano)ethenes (3a–3e)
3.1.2. General Procedure for the Synthesis of the 2-aryl-4,5-dicyano-1H-imidazoles (4a–4d)
3.2. Antioxidant Capacity
3.2.1. Cyclic Voltammetry Technique
3.2.2. DPPH Radical Method
3.2.3. Deoxyribose Degradation Method
3.3. Determination of Antifungal Activity
3.4. Analysis of Toxicity in Mammalian Fibroblast
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Compound | R1 | R2 | R3 | R4 | Reaction Conditions | Yield (%) |
---|---|---|---|---|---|---|
3a | OH | H | H | H | 1 + 2a (1.0 equiv.), EtOH, H2SO4, r.t., 10 min | 97 |
3b | H | OH | H | H | 1 + 2b (1.0 equiv.), EtOH, H2SO4, r.t., 10 min | 82 |
3c | H | H | OH | H | 1 + 2c (1.0 equiv.), EtOH, H2SO4, r.t., 10 min | 87 |
3d | H | OH | OH | H | 1 + 2d (1.0 equiv.), EtOH, H2SO4, r.t., 10 min | 81 |
3e | H | OH | OH | OH | 1 + 2e (1.0 equiv.), EtOH, H2SO4, r.t., 10 min | 92 |
4a | OH | H | H | H | 3a, ethyl acetate/acetonitrile, MnO2, reflux, 14 h | 50 |
4b | H | OH | H | H | 3b, ethyl acetate/acetonitrile, MnO2, reflux, 5 days | 70 |
4c | H | H | OH | H | 3c, ethyl acetate/acetonitrile, MnO2, reflux, 8 days | 63 |
4d | H | OH | OH | H | 3d, ethyl acetate/acetonitrile, MnO2, reflux, 24 h | 55 |
Compound | Ep (mV vs. ECS) | Ep/2 (mV vs. ECS) | DPPH IC50 (μM) | % Inhibition of deoxyribose degradation |
---|---|---|---|---|
3a | 688 | 649 | n.d. | n.d. |
3b | 740 | - | n.d. | n.d. |
3c | 476 | 361 | n.d. | n.d. |
3d | 248 | 185 | n.d. | n.d. |
3e | 113 | 40 | 3.7 ± 0.7 | 62.1 ± 2.3 |
4a | 783 | 758 | n.d. | n.d. |
4b | 896 | 712 | n.d. | n.d. |
4c | 620 | 534 | n.d. | n.d. |
4d | 254 | 166 | 12.0 ± 1.0 | 59.0 ± 3.5 |
Trolox | 173 | 107 | 9.0 ± 0.2 | 23.4 ± 2.6 |
Compound | Antifungal Activity MIC (μM) | Cellular Viability (%) | |
---|---|---|---|
Saccharomyces cerevisiae | Candida albicans | Fibroblasts | |
3a | >200.0 * | >200.0 * | n.d. |
3b | >200.0 * | >200.0 * | n.d. |
3c | >400.0 * | >400.0 * | n.d. |
3d | >400.0* | >400.0 * | n.d. |
3e | 50.0 | 100.0 | 97.3 ± 1.9 |
4a | >400.0 * | >400.0 * | n.d. |
4b | >400.0 * | >400.0 * | n.d. |
4c | >400.0 * | >400.0 * | n.d. |
4d | 400.0 | 600.0 | 94.8 ± 3.5 |
Miconazole | 100.0 | 0.78 | n.d. |
Fluconazole | 50 | 1.56 | n.d. |
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Bettencourt, A.; Castro, M.; Silva, J.; Fernandes, F.; Coutinho, O.; Sousa, M.J.; Proença, M.F.; Areias, F. New Nitrogen Compounds Coupled to Phenolic Units with Antioxidant and Antifungal Activities: Synthesis and Structure–Activity Relationship. Molecules 2018, 23, 2530. https://doi.org/10.3390/molecules23102530
Bettencourt A, Castro M, Silva J, Fernandes F, Coutinho O, Sousa MJ, Proença MF, Areias F. New Nitrogen Compounds Coupled to Phenolic Units with Antioxidant and Antifungal Activities: Synthesis and Structure–Activity Relationship. Molecules. 2018; 23(10):2530. https://doi.org/10.3390/molecules23102530
Chicago/Turabian StyleBettencourt, Ana, Marián Castro, João Silva, Francisco Fernandes, Olga Coutinho, M. João Sousa, M. Fernanda Proença, and Filipe Areias. 2018. "New Nitrogen Compounds Coupled to Phenolic Units with Antioxidant and Antifungal Activities: Synthesis and Structure–Activity Relationship" Molecules 23, no. 10: 2530. https://doi.org/10.3390/molecules23102530