Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Crystal Structure
2.3. In Vitro Antifungal Activity Analysis
2.4. Morphological Study of G. saubinetii Fungus with SEM
2.5. Morphological Study of G. saubinetii Fungus with FM
2.6. Mechanistic Study of the Antifungal Activity of E13
3. Materials and Methods
3.1. Instruments and Chemicals
3.2. Fungi
3.3. Crystallographic Analysis
3.4. General Procedure for the Synthesis of Intermediate B
3.5. General Synthesis Procedure for Intermediates C and D
3.6. General Synthesis Procedure for Target Compounds E1–E28
3.7. In Vitro Antifungal Activity
3.8. Morphological Observation of G. saubinetii by Scanning Electron Microscopy
3.9. Morphological Observation of G. saubinetii by Fluorescence Microscope
3.10. Determination of Cytoplasmic Content Leakage
3.11. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound No. | Inhibition Rate ± SD (%) | ||||||
---|---|---|---|---|---|---|---|
GS | VD | SS | FO | FP | TC | PC | |
E1 | 69.9 ± 2.0 | 73.8 ± 3.0 | 88.8 ± 2.3 | 59.1 ± 0.9 | 57.1 ± 0.5 | 65.8 ± 0.8 | 29.2 ± 1.3 |
E2 | 69.6 ± 1.1 | 69.4 ± 0.9 | 71.8 ± 3.9 | 10.9 ± 2.7 | 30.3 ± 0.8 | 45.8 ± 1.7 | 39.8 ± 0.5 |
E3 | 0 | 16.1 ± 0.5 | 11.3 ± 0.5 | 0 | 11.2 ± 0.5 | 48.3 ± 2.2 | 11.1 ± 1.8 |
E4 | 27.5 ± 2.0 | 22.1 ± 0.5 | 21.7 ± 4.0 | 0 | 15.6 ± 0.8 | 25.3 ± 2.4 | 23.7 ± 0.9 |
E5 | 24.5 ± 0.0 | 22.4 ± 1.1 | 11.9 ± 1.9 | 54.2 ± 0.5 | 58.2 ± 0.8 | 84.9 ± 0.5 | 36.6 ± 3.3 |
E6 | 64.1 ± 0.6 | 93.8 ± 1.9 | 49.4 ± 0.5 | 9.4 ± 4.1 | 33.1 ± 0.5 | 67.5 ± 1.7 | 32.8 ± 2.2 |
E7 | 75.3 ± 2.9 | 80.3 ± 2.8 | 72.4 ± 1.7 | 35.8 ± 0.5 | 56.6 ± 0.8 | 81.4 ± 1.3 | 62.3 ±0.9 |
E8 | 64.1 ± 1.0 | 50.6 ± 0.5 | 83.1 ± 2.6 | 11.2 ± 0.5 | 28.1 ± 1.0 | 24.7 ± 1.7 | 17.3 ± 0.5 |
E9 | 59.8 ± 0.5 | 83.0 ± 1.9 | 92.8 ± 0.5 | 8.2 ± 0.9 | 38.9 ± 1.3 | 19.7 ± 2.6 | 26.9 ± 1.3 |
E10 | 78.5 ± 0.3 | 91.8 ± 2.2 | 87.5 ± 0.0 | 69.4 ± 1.4 | 68.3 ± 0.5 | 81.1 ± 1.1 | 53.8 ± 1.0 |
E11 | 65.7 ± 0.0 | 75.2 ± 0.5 | 68.8 ± 2.7 | 8.8 ± 2.3 | 21.0 ± 3.1 | 41.4 ± 5.4 | 5.0 ± 0.5 |
E12 | 48.7 ± 0.6 | 65.2 ± 0.5 | 54.5 ± 1.8 | 33.3 ± 1.4 | 38.3 ± 0.5 | 28.1 ± 1.3 | 46.5 ± 0.9 |
E13 | 78.3 ± 0.9 | 100 | 92.5 ± 0.8 | 70.3 ± 0.5 | 69.7 ± 0.8 | 87.5 ± 0.0 | 76.3 ± 1.5 |
E14 | 80.2 ± 0.9 | 95.9 ± 1.4 | 71.9 ± 3.8 | 68.8 ± 1.1 | 69.1 ± 1.3 | 66.9 ± 0.5 | 70.2 ± 1.8 |
E15 | 37.9 ± 0.6 | 23.6 ± 0.0 | 34.2 ± 1.4 | 27.3 ± 1.6 | 49.5 ± 2.4 | 60.8 ± 1.7 | 61.1 ± 2.0 |
E16 | 42.3 ± 1.3 | 39.3 ± 1.0 | 24.9 ± 1.1 | 27.0 ± 1.0 | 31.8 ± 0.8 | 49.2 ± 0.7 | 35.1 ± 0.9 |
E17 | 69.5 ± 2.2 | 83.3 ± 2.2 | 89.7 ± 0.5 | 10.0 ± 1.8 | 12.3 ± 0.7 | 18.1 ± 0.5 | 58.2 ± 1.0 |
E18 | 73.3 ± 1.7 | 81.3 ± 1.8 | 69.0 ± 0.9 | 0 | 24.3 ± 2.5 | 48.1 ± 0.5 | 37.7 ± 1.5 |
E19 | 66.0 ± 2.5 | 67.9 ± 0.0 | 69.7 ± 0.5 | 52.4 ± 1.0 | 39.3 ± 0.9 | 57.3 ± 0.8 | 48.8 ± 0.5 |
E20 | 76.0 ± 1.9 | 94.4 ± 0.0 | 80.5 ± 0.5 | 69.0 ± 2.5 | 69.7 ± 1.7 | 65.9 ± 1.0 | 74.2 ± 0.9 |
E21 | 65.1 ± 0.6 | 81.8 ± 1.9 | 77.3 ± 0.5 | 24.9 ± 2.6 | 60.9 ± 0.5 | 61.2 ± 1.1 | 8.5 ± 1.0 |
E22 | 71.6 ± 1.1 | 64.2 ± 0.6 | 67.9 ± 0.5 | -- | -- | -- | -- |
E23 | 72.2 ± 1.0 | 80.6 ± 0.6 | 52.5 ± 0.5 | -- | -- | -- | -- |
E24 | 74.1 ± 1.0 | 81.6 ± 0.6 | 65.1 ± 2.8 | -- | -- | -- | -- |
E25 | 71.9 ± 0.6 | 78.2 ± 1.6 | 57.1 ± 1.1 | -- | -- | -- | -- |
E26 | 73.8 ± 0.6 | 80.9 ± 1.0 | 61.7 ± 1.4 | -- | -- | -- | -- |
E27 | 74.4 ± 2.0 | 68.6 ± 1.5 | 74.1 ± 0.9 | -- | -- | -- | -- |
E28 | 76.0 ± 1.0 | 74.6 ± 0.6 | 67.9 ± 0.5 | -- | -- | -- | -- |
MP | 19.1 ± 0.4 | 27.2 ± 0.9 | 14.0 ± 0.5 | 26.5 ± 0.9 | 27.5 ± 1.1 | 23.6 ± 1.9 | 25.2 ± 1.0 |
HY | -- | -- | -- | -- | -- | 79.3 ± 1.6 | 69.6 ± 0.5 |
Compound No. | EC50 (mg/L) | ||||
---|---|---|---|---|---|
GS | VD | SS | TC | PC | |
E1 | 47.4 ± 2.6 | 50.7 ± 2.8 | 23.0 ± 1.5 | -- | -- |
E2 | 37.3 ± 1.4 | 37.2 ± 1.2 | 27.1 ± 1.5 | -- | -- |
E5 | -- | -- | -- | 18.5 ± 0.4 | -- |
E6 | 49.9 ± 0.4 | 12.7 ± 0.5 | 90.5 ± 3.5 | -- | -- |
E7 | 30.6 ± 3.0 | 14.3 ± 0.1 | 40.1 ± 2.7 | 5.7 ± 0.2 | -- |
E8 | 79.1 ± 2.6 | >100 | 13.8 ± 3.1 | -- | -- |
E9 | 24.6 ± 0.7 | 29.0 ± 2.1 | 10.3 ± 1.0 | -- | -- |
E10 | 29.4 ± 0.6 | 37.2 ± 1.0 | 21.9 ± 0.4 | 36.3 ± 1.3 | -- |
E13 | 20.4 ± 1.3 | 18.5 ± 1.2 | 33.5 ± 1.8 | 7.1 ± 0.1 | 42.9 ± 0.7 |
E14 | 21.5 ± 1.0 | 23.1 ± 0.8 | 37.6 ± 1.9 | -- | 49.3 ± 1.4 |
E17 | 22.0 ± 1.5 | 16.1 ± 0.2 | 27.9 ± 0.2 | -- | -- |
E18 | 24.5 ± 0.9 | 15.8 ± 1.4 | 8.0 ± 0.3 | -- | -- |
E19 | 56.1 ± 0.9 | 65.7 ± 0.7 | 47.8 ± 1.7 | -- | -- |
E20 | 31.6 ± 0.6 | 29.6 ± 2.3 | 39.1 ± 1.1 | -- | 50.9 ± 1.4 |
E21 | 27.3 ± 2.0 | 13.4 ± 0.6 | 36.3 ± 0.3 | 37.6 ± 1.0 | -- |
E22 | 51.1 ± 0.2 | 61.3 ± 1.6 | 48.5 ± 0.4 | -- | -- |
E23 | 32.5 ± 0.9 | 32.3 ± 0.4 | 81.4 ± 2.1 | -- | -- |
E24 | 30.8 ± 1.5 | 38.5 ± 1.0 | 51.6 ± 5.4 | -- | -- |
E25 | 31.3 ± 1.5 | 33.7 ± 3.5 | 75.2 ± 3.4 | -- | -- |
E26 | 32.7 ± 1.1 | 30.4 ± 1.3 | 54.0 ± 1.8 | -- | -- |
E27 | 25.2 ± 1.0 | 43.0 ± 1.6 | 37.2 ± 0.8 | -- | -- |
E28 | 24.2 ± 0.4 | 26.9 ± 0.2 | 47.9 ± 0.2 | -- | -- |
MP | >100 | >100 | >100 | -- | -- |
HY | -- | -- | -- | 13.8 ± 1.5 | 17.9 ± 1.3 |
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Chen, B.; Song, D.; Shi, H.; Chen, K.; Wu, Z.; Chai, H. Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives. Int. J. Mol. Sci. 2023, 24, 8898. https://doi.org/10.3390/ijms24108898
Chen B, Song D, Shi H, Chen K, Wu Z, Chai H. Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives. International Journal of Molecular Sciences. 2023; 24(10):8898. https://doi.org/10.3390/ijms24108898
Chicago/Turabian StyleChen, Biao, Dandan Song, Huabin Shi, Kuai Chen, Zhibing Wu, and Huifang Chai. 2023. "Design, Synthesis, In Vitro Antifungal Activity and Mechanism Study of the Novel 4-Substituted Mandelic Acid Derivatives" International Journal of Molecular Sciences 24, no. 10: 8898. https://doi.org/10.3390/ijms24108898