Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Antifungal Activity
2.3. Qualitative Structure–Activity Relationship
3. Experimental Section
3.1. General
3.2. Synthesis of Title Compounds
3.2.1. N′-(4-((4aS,5S,5aR)-5a-Methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)acetohydrazide (6a)
3.2.2. 2-Cyano-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)acetohydrazide (6b)
3.2.3. N′1, N′2-Bis(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclo-propa[f]benzofuran- 5-yl)butan-2-ylidene)oxalohydrazide (6c)
3.2.4. N′-(4-((4aS,5S,5aR)-5a-Methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]-benzofuran- 5-yl)butan-2-ylidene)thiophene-2-carbohydrazide (6d)
3.2.5. 5-Chloro-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)thiophene-2-carbohydrazide (6e)
3.2.6. 5-Bromo-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclo-propa[f]benzofuran- 5-yl)butan-2-ylidene)thiophene-2-carbohydrazide (6f)
3.2.7. N′-(4-((4aS,5S,5aR)-5a-Methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]-benzofuran- 5-yl)butan-2-ylidene)nicotinohydrazide (6g)
3.2.8. 4-Amino-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclo-propa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6h)
3.2.9. 4-Hydroxy-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6i)
3.2.10. 2-Hydroxy-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzo -furan-5-yl)butan-2-ylidene)benzohydrazide (6j)
3.2.11. 2-Chloro-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6k)
3.2.12. 3-Chloro-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6l)
3.2.13. N′-(4-((4aS,5S,5aR)-5a-Methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]-benzofuran- 5-yl)butan-2-ylidene)-4-nitrobenzohydrazide (6m)
3.2.14. 4-Cyano-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6n)
3.2.15. 3-Methyl-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6o)
3.2.16. 4-Methoxy-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6p)
3.2.17. 3-Methoxy-N′-(4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzohydrazide (6q)
3.2.18. N′-((E)-4-((4aS,5S,5aR)-5a-Methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)benzenesulfonohydrazide (7r)
3.2.19. 4-Methyl-N′-((E)-4-((4aS,5S,5aR)-5a-methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran-5-yl)butan-2-ylidene)benzenesulfonohydrazide (7s)
3.2.20. (4aS,5S,5aR)-5-(3-(2-(2-Hydroxyethyl)hydrazono)butyl)-5a-methyl-3-methyl-eneoctahydro- 2H-cyclopropa[f]benzofuran-2-one (8a)
3.2.21. (4aS,5S,5aR)-5a-Methyl-3-methylene-5-(3-(2-phenylhydrazono)butyl)-octa-hydro-2H-cyclopropa[ f]benzofuran-2-one (8b)
3.2.22. (4aS,5S,5aR)-5a-Methyl-3-methylene-5-(3-(2-(2,4,6-trichlorophenyl)-hydrazono)butyl)- octahydro-2H-cyclopropa[f]benzofuran-2-one (8c)
3.2.23. (4aS,5S,5aR)-5a-Methyl-3-methylene-5-(3-(2-(4-nitrophenyl)hydrazono)-butyl)-octahydro-2H-cyclopropa[ f]benzofuran-2-one (8d)
3.2.24. (4aS,5S,5aR)-5a-Methyl-3-methylene-5-(3-(2-(2-nitrophenyl)hydrazono)butyl)-octahydro-2H-cyclopropa[ f]benzofuran-2-one (8e)
3.2.25. (4aS,5S,5aR)-5a-Methyl-3-methylene-5-(3-(2-(4-(trifluoromethyl)phenyl)-hydrazono)butyl)- octahydro-2H-cyclopropa[f]benzofuran-2-one (8f)
3.2.26. (4aS,5S,5aR)-5a-Methyl-3-methylene-5-(3-(2-(2,3,5,6-tetrafluorophenyl)-hydrazono)butyl)- octahydro-2H-cyclopropa[f]benzofuran-2-one (8g)
3.2.27. (4aS,5S,5aR)-5-(3-(2-(5,6-Dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazono)-butyl)-5a-methyl- 3-methyleneoctahydro-2H-cyclopropa[f]benzofuran-2-one (8h)
3.2.28. 4-(2-(4-((4aS,5S,5aR)-5a-Methyl-3-methylene-2-oxooctahydro-2H-cyclopropa[f]benzofuran- 5-yl)butan-2-ylidene)hydrazinyl)benzoic acid (8i)
3.3. Microorganism and Preparation of Spore Suspension
3.4. Spore Germination Assay
3.5. Preparation of Tested Tomato Fruits
3.6. Culture of B. cinerea and Inoculation
3.7. Statistical Analysis
4. Conclusions
Supplementary Information
ijms-15-04257-s001.pdfAcknowledgments
Conflicts of Interest
- Author ContributionsWang Hao designed and conducted the experiment and wrote the paper; Ren Shuang-Xi and Wang De-Long assisted in the completion of synthesis of the title compounds; He Ze-Yu and Yan Xiao-Nan took part in the experiments on activity evaluation; Feng Jun-Tao and Zhang Xing supervised the whole experiment and provided technical guidance. All the authors contributed to the analysis of the data.
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Compound No. | Yield a (%) | In vitro (IC50 b, μg/mL) | In vivo (IC50 b, μg/mL) | |
---|---|---|---|---|
B. cinerea | C. lagenarium | B. cinerea | ||
6a | 78 | 27.33 ± 1.29 | 10.18 ± 1.02 | 29.62 ± 3.12 |
6b | 82 | 9.77 ± 0.68 | 8.14 ± 0.34 | 7.55 ± 0.68 |
6c | 93 | 22.07 ± 0.70 | 10.22 ± 0.62 | 30.80 ± 1.51 |
6d | 78 | 7.81 ± 0.37 | 10.83 ± 1.79 | 12.84 ± 0.31 |
6e | 87 | 5.57 ± 0.89 | 9.98 ± 0.30 | 9.57 ± 0.99 |
6f | 72 | 4.83 ± 0.41 | 10.02 ± 0.72 | 7.03 ± 0.58 |
6g | 70 | 8.50 ± 0.69 | 2.06 ± 0.86 | 4.02 ± 0.26 |
6h | 78 | 2.67 ± 0.10 | 2.10 ± 0.19 | 4.85 ± 0.52 |
6i | 59 | 3.46 ± 0.39 | 1.24 ± 0.47 | 4.73 ± 1.13 |
6j | 48 | 13.16 ± 0.23 | 2.01 ± 0.34 | 13.44 ± 1.02 |
6k | 77 | 3.35 ± 0.65 | 3.52 ± 0.21 | 9.67 ± 0.95 |
6l | 78 | 2.57 ± 0.12 | 1.97 ± 0.78 | 8.76 ± 1.08 |
6m | 61 | 3.39 ± 0.56 | 5.49 ± 0.73 | 6.67 ± 0.49 |
6n | 88 | 2.47 ± 0.72 | 1.69 ± 0.54 | 4.29 ± 0.51 |
6o | 65 | 9.00 ± 1.09 | 0.98 ± 0.19 | 18.08 ± 0.91 |
6p | 53 | 10.30 ± 0.86 | 2.56 ± 0.32 | 16.42 ± 1.24 |
6q | 47 | 6.37 ± 0.71 | 0.77 ± 0.27 | 12.52 ± 0.96 |
7r | 66 | 13.32 ± 0.87 | 6.43 ± 0.95 | 17.46 ± 0.88 |
7s | 73 | 12.99 ± 0.62 | 5.33 ± 0.89 | 17.26 ± 1.05 |
8a | 58 | 17.37 ± 0.91 | 15.23 ± 1.14 | 16.69 ± 2.37 |
8b | 47 | 16.32 ± 0.58 | 7.62 ± 0.19 | 18.85 ± 1.25 |
8c | 75 | 1.51 ± 0.73 | 1.53 ± 0.46 | 2.10 ± 0.47 |
8d | 65 | 3.79 ± 0.82 | 3.95 ± 0.28 | 4.62 ± 0.29 |
8e | 77 | 10.31 ± 1.31 | 4.27 ± 0.35 | 8.93 ± 0.96 |
8f | 72 | 1.99 ± 0.34 | 4.05 ± 0.57 | 5.52 ± 0.37 |
8g | 63 | 1.27 ± 0.16 | 2.65 ± 0.91 | 2.59 ± 0.63 |
8h | 81 | 13.32 ± 0.87 | 1.63 ± 0.45 | 11.46 ± 1.09 |
8i | 45 | 14.77 ± 0.59 | 7.06 ± 0.77 | 14.59 ± 0.95 |
Carabrone | 14.14 ± 0.94 | 8.29 ± 0.51 | 16.74 ± 1.32 | |
Chlorothalonil c | 0.49 ± 0.28 | 0.52 ± 0.17 | 1.29 ± 0.33 |
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Wang, H.; Ren, S.-X.; He, Z.-Y.; Wang, D.-L.; Yan, X.-N.; Feng, J.-T.; Zhang, X. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents. Int. J. Mol. Sci. 2014, 15, 4257-4272. https://doi.org/10.3390/ijms15034257
Wang H, Ren S-X, He Z-Y, Wang D-L, Yan X-N, Feng J-T, Zhang X. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents. International Journal of Molecular Sciences. 2014; 15(3):4257-4272. https://doi.org/10.3390/ijms15034257
Chicago/Turabian StyleWang, Hao, Shuang-Xi Ren, Ze-Yu He, De-Long Wang, Xiao-Nan Yan, Jun-Tao Feng, and Xing Zhang. 2014. "Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents" International Journal of Molecular Sciences 15, no. 3: 4257-4272. https://doi.org/10.3390/ijms15034257