Microwave-Assisted Synthesis of Aminophosphonic Derivatives and Their Antifungal Evaluation against Lomentospora prolificans
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. In Vitro Assays
2.3. Antifungal Activity Evaluation (M38-A2 Protocol)
2.4. Molecular Docking
2.5. Cytotoxicity
3. Materials and Methods
3.1. Synthesis of α-Aminophosphonates 5–16
- (E)-ethyl 4-((1-(diphenoxyphosphoryl)-3-phenylallyl)amino)benzoate (5)
- (E)-ethyl 4-((3-(4-(dimethylamino)phenyl)-1-(diphenoxyphosphoryl)allyl)amino) benzoate (6)
- Ethyl 4-(((4-(dimethylamino)phenyl)(diphenoxyphosphoryl)methyl)amino)benzoate (7)
- Ethyl 4-(((4-(diethylamino)phenyl)(diphenoxyphosphoryl)methyl)amino)benzoate (8)
- Ethyl 4-(((diphenoxyphosphoryl)(thiophen-2-yl)methyl)amino)benzoate (9)
- (E)-diphenyl (3-phenyl-1-(phenylamino)allyl)phosphonate (10)
- Diphenyl ((4-(dimethylamino)phenyl)(phenylamino)methyl)phosphonate (11)
- Diphenyl ((phenylamino)(thiophen-2-yl)methyl)phosphonate (12)
- (E)-diphenyl (1-((4-cyanophenyl)amino)-3-phenyl allyl)phosphonate (13)
- (E)-diphenyl(1-((4-cyanophenyl)amino)-3-(4-(dimethylamino)phenyl)allyl)phosphonate (14)
- Diphenyl (((4-cyanophenyl)amino)(4-(dimethylamino)phenyl)methyl)phosphonate (15)
- Diphenyl (((4-cyanophenyl)amino)(4-(diethylamino)phenyl)methyl)phosphonate (16)
3.2. Synthesis of α-Aminophosphonic Acids 17–28
- (E)-ethyl 4-((1-(hydroxy(phenoxy)phosphoryl)-3-phenylallyl)amino)benzoate (17)
- (E)-ethyl 4-((3-(4-(dimethylamino)phenyl)-1-(hydroxy(phenoxy)phosphoryl)allyl) amino)benzoate (18)
- Ethyl 4-(((4-(dimethylamino)phenyl)(hydroxy(phenoxy)phosphoryl)methyl)amino)benzoate (19)
- Ethyl 4-(((4-(diethylamino)phenyl)(hydroxy(phenoxy)phosphoryl)methyl)amino) benzoate (20)
- Ethyl 4-(((hydroxy(phenoxy)phosphoryl)(thiophen-2-yl)methyl)amino)benzoate (21)
- (E)-phenyl hydrogen (3-phenyl-1-(phenylamino)allyl)phosphonate (22)
- Phenyl hydrogen ((phenylamino)(thiophen-2-yl)methyl)phosphonate (23)
- (E)-phenyl hydrogen (1-((4-cyanophenyl)amino)-3-phenylallyl)phosphonate (24)
- (E)-phenyl hydrogen (1-((4-cyanophenyl)amino)-3-(4-(dimethylamino)phenyl)allyl) phosphonate (25)
- Phenyl hydrogen (((4-cyanophenyl)amino)(4-(dimethylamino)phenyl)methyl)phosphonate (26)
- Phenyl hydrogen (((4-cyanophenyl)amino)(4-(diethylamino)phenyl)methyl) phosphonate (27)
- Phenyl hydrogen ((4-(dimethylamino)phenyl)(phenylamino)methyl)phosphonate (28)
3.3. In Vitro Antifungal Activity
3.4. Evaluation of Cytotoxic Activity
3.4.1. Cell Culture
3.4.2. MTT Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Comp | JH-P | JC-P | Comp | JH-P | JC-P | Comp | JH-P | JC-P | Comp | JH-P | JC-P |
---|---|---|---|---|---|---|---|---|---|---|---|
5 | 25.85 | 156.26 | 11 | 23.73 | 156.74 | 17 | 24.6 | 142.97 | 23 | 20.36 | 142.24 |
6 | 25.72 | 157.1 | 12 | 25.12 | 164.28 | 18 | 22.2 | 140.86 | 24 | 23.6 | 144.0 |
7 | 23.5 | 157.07 | 13 | 25.36 | 156.82 | 19 | 21.31 | 138.44 | 25 | 24.26 | 142.4 |
8 | 23.31 | 157.47 | 14 | 24.37 | 157.53 | 20 | 20.62 | 140.06 | 26 | 24.25 | 143.34 |
9 | 24.02 | 162.6 | 15 | 23.65 | 157.9 | 21 | 21.23 | 157.7 | 27 | 21.98 | 142.1 |
10 | 26.11 | 155.71 | 16 | 23.44 | 158.11 | 22 | 23.39 | 142.8 | 28 | 20.36 | 142.24 |
Strain | MIC100 Range (μg/mL) Compound 7 | MIC100 Range (μg/mL) Compound 11 | MIC100 Range (μg/mL) Compound 13 | MIC100 Range (μg/mL) Compound 22 | MIC100 Range (μg/mL) Compound 27 | MIC100 Range (μg/mL) VRC |
---|---|---|---|---|---|---|
L. prolificans (5) | 900->900 | 900->900 | 900->900 | 900->900 | 900->900 | 16->16 |
Compound (1000 µM) | Viability (%) |
---|---|
7 | 39.01 ± 2.45 |
11 | 38.72 ± 1.31 |
13 | 41.85 ± 3.13 |
22 | 67.91 ± 4.85 |
27 | 60.26 ± 3.15 |
Voriconazole | 68.55 ± 2.05 |
Etoposide * | 40.79 ± 2.56 |
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Martínez-Campos, Z.; Elizondo-Zertuche, M.; Hernández-Núñez, E.; Hernández-Fernández, E.; Robledo-Leal, E.; López-Cortina, S.T. Microwave-Assisted Synthesis of Aminophosphonic Derivatives and Their Antifungal Evaluation against Lomentospora prolificans. Molecules 2023, 28, 3995. https://doi.org/10.3390/molecules28103995
Martínez-Campos Z, Elizondo-Zertuche M, Hernández-Núñez E, Hernández-Fernández E, Robledo-Leal E, López-Cortina ST. Microwave-Assisted Synthesis of Aminophosphonic Derivatives and Their Antifungal Evaluation against Lomentospora prolificans. Molecules. 2023; 28(10):3995. https://doi.org/10.3390/molecules28103995
Chicago/Turabian StyleMartínez-Campos, Zuleyma, Mariana Elizondo-Zertuche, Emanuel Hernández-Núñez, Eugenio Hernández-Fernández, Efrén Robledo-Leal, and Susana T. López-Cortina. 2023. "Microwave-Assisted Synthesis of Aminophosphonic Derivatives and Their Antifungal Evaluation against Lomentospora prolificans" Molecules 28, no. 10: 3995. https://doi.org/10.3390/molecules28103995