Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Docking Analysis
2.2. Chemistry
2.3. Herbicidal Activity
2.4. Crystal Structure Determination of Compound 3a
2.5. PPO Enzyme Assays
3. Materials and Methods
3.1. Molecular Docking
3.2. Equipment and Materials
3.3. General Synthetic Procedure for Compounds 3
3.4. Herbicidal Activity
3.5. PPO Enzyme Assays
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Compd. | Affinity | Compd. | Affinity | Compd. | Affinity | Compd. | Affinity |
---|---|---|---|---|---|---|---|
3a | −10.0 | 3h | −8.7 | 3o | −9.5 | 3v | −8.1 |
3b | −8.6 | 3i | −8.4 | 3p | −8.7 | 3w | −7.7 |
3c | −10.1 | 3j | −7.7 | 3q | −9.3 | 3x | −9.8 |
3d | −9.1 | 3k | −9.4 | 3r | −9.0 | 3y | −9.5 |
3e | −9.8 | 3l | −8.9 | 3s | −10.2 | Flumioxazin | −9.5 |
3f | −9.7 | 3m | −9.9 | 3t | −9.7 | Chlortoluron | −7.1 |
| ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Compd. | R1 | R2 | Ar | Yield (%) | Compd. | R1 | R2 | Ar | Yield (%) | Compd. | R1 | R2 | Ar | Yield (%) |
3a | H | H | | 73 | 3j | Cl | H | | 71 | 3s | F | H | | 79 |
3b | H | Cl | | 77 | 3k | Cl | H | | 63 | 3t | H | Cl | | 79 |
3c | Cl | H | | 81 | 3l | Cl | H | | 86 | 3u | H | Cl | | 70 |
3d | Cl | H | | 28 | 3m | Cl | H | | 84 | 3v | H | Cl | | 76 |
3e | Cl | H | | 80 | 3n | Cl | H | | 52 | 3w | H | Cl | | 79 |
3f | Cl | H | | 78 | 3o | Cl | H | | 87 | 3x | H | CH3 | | 47 |
3g | Cl | H | | 58 | 3p | Cl | H | | 30 | 3y | H | NO2 | | 57 |
3h | Cl | H | | 60 | 3q | F | H | | 57 | |||||
3i | Cl | H | | 67 | 3r | F | H | | 78 |
Compd. | BCa | ARa | DSa | |||
---|---|---|---|---|---|---|
Root | Stem | Root | Stem | Root | Stem | |
3a | 92 ± 1 | 61 ± 2 | 37 ± 1 | 87 ± 2 | 68 ± 3 | 83 ± 2 |
3b | 74 ± 2 | 0 | 28 ± 4 | 66 ± 4 | 77 ± 2 | 62 ± 3 |
3c | 78 ± 5 | 0 | 65 ± 1 | 22 ± 1 | 61 ± 1 | 0 |
3d | 82 ± 1 | 35 ± 1 | 81 ± 4 | 33 ± 2 | 65 ± 2 | 10 ± 1 |
3e | 28 ± 2 | 21 ± 2 | 51 ± 1 | 55 ± 3 | 28 ± 2 | 38 ± 3 |
3f | 46 ± 2 | 73 ± 3 | 68 ± 0 | 42 ± 0 | 47 ± 3 | 0 |
3g | 0 | 18 ± 0 | 74 ± 2 | 41 ± 2 | 91 ± 1 | 83 ± 1 |
3h | 77 ± 3 | 0 | 62 ± 2 | 33 ± 1 | 55 ± 1 | 34 ± 1 |
3i | 58 ± 4 | 0 | 55 ± 1 | 27 ± 2 | 67 ± 5 | 17 ± 3 |
3j | 75 ± 0 | 0 | 66 ± 1 | 34 ± 1 | 87 ± 2 | 11 ± 0 |
3k | 65 ± 1 | 0 | 53 ± 3 | 36 ± 2 | 57 ± 1 | 0 |
3l | 68 ± 2 | 6 ± 2 | 44 ± 3 | 31 ± 2 | 48 ± 4 | 51 ± 3 |
3m | 45 ± 3 | 0 | 55 ± 4 | 45 ± 3 | 57 ± 2 | 0 |
3n | 49 ± 1 | 0 | 59 ± 2 | 33 ± 2 | 59 ± 4 | 0 |
3o | 89 ± 1 | 77 ± 0 | 83 ± 5 | 51 ± 3 | 63 ± 4 | 0 |
3p | 51 ± 2 | 9 ± 2 | 37 ± 3 | 72 ± 4 | 58 ± 1 | 45 ± 2 |
3q | 28 ± 1 | 22 ± 1 | 22 ± 1 | 21 ± 2 | 38 ± 3 | 0 |
3r | 65 ± 4 | 54 ± 3 | 62 ± 2 | 75 ± 3 | 87 ± 2 | 86 ± 2 |
3s | 64 ± 2 | 15 ± 1 | 35 ± 4 | 61 ± 5 | 53 ± 3 | 28 ± 5 |
3t | 54 ± 1 | 0 | 16 ± 1 | 39 ± 4 | 46 ± 2 | 18 ± 1 |
3u | 77 ± 1 | 53 ± 3 | 0 | 53 ± 2 | 51 ± 2 | 32 ± 1 |
3v | 60 ± 5 | 0 | 10 ± 2 | 42 ± 3 | 22 ± 1 | 21 ± 2 |
3w | 58 ± 2 | 0 | 28 ± 1 | 61 ± 2 | 79 ± 2 | 11 ± 2 |
3x | 59 ± 4 | 0 | 36 ± 3 | 55 ± 3 | 31 ± 2 | 24 ± 1 |
3y | 68 ± 2 | 9 ± 0 | 34 ± 4 | 60 ± 4 | 44 ± 1 | 37 ± 3 |
Chlortoluron | 85 ± 4 | 58 ± 3 | 92 ± 3 | 90 ± 5 | 98 ± 0 | 97 ± 1 |
Atrazine | 81 ± 1 | 52 ± 1 | 32 ± 2 | 66 ± 2 | 58 ± 1 | 60 ± 2 |
Flumioxazin | 85 ± 3 | 72 ± 5 | 82 ± 2 | 88 ± 1 | 71 ± 2 | 91 ± 0 |
Compd. | BC | AR | DS | Compd. | BC | AR | DS |
---|---|---|---|---|---|---|---|
3a | 25 ± 2 | 82 ± 3 | 37 ± 1 | 3o | 16 ± 2 | 27 ± 2 | 23 ± 2 |
3b | 27 ± 2 | 18 ± 2 | 12 ± 1 | 3p | 19 ± 4 | 20 ± 1 | 14 ± 0 |
3c | 48 ± 1 | 13 ± 1 | 19 ± 3 | 3q | 30 ± 2 | 19 ± 2 | 36 ± 1 |
3d | 60 ± 3 | 73 ± 2 | 20 ± 1 | 3r | 37 ± 1 | 22 ± 3 | 36 ± 5 |
3e | 35 ± 4 | 47 ± 3 | 33 ± 1 | 3s | 22 ± 1 | 44 ± 2 | 18 ± 1 |
3f | 56 ± 1 | 10 ± 2 | 11 ± 1 | 3t | 29 ± 2 | 62 ± 3 | 17 ± 1 |
3g | 38 ± 2 | 0 | 23 ± 2 | 3u | 60 ± 2 | 5 ± 1 | 28 ± 2 |
3h | 58 ± 1 | 7 ± 1 | 27 ± 2 | 3v | 33 ± 1 | 0 | 0 |
3i | 28 ± 2 | 34 ± 2 | 37 ± 1 | 3w | 35 ± 1 | 22 ± 4 | 36 ± 4 |
3j | 23 ± 2 | 20 ± 5 | 31 ± 1 | 3x | 17 ± 2 | 7 ± 2 | 7 ± 1 |
3k | 35 ± 5 | 24 ± 3 | 0 | 3y | 28 ± 1 | 0 | 0 |
3l | 33 ± 1 | 37 ± 2 | 26 ± 2 | Chlortoluron | nd a | 91 ± 1 | 65 ± 2 |
3m | 22 ± 4 | 35 ± 1 | 34 ± 2 | Atrazine | nd a | 91 ± 2 | 47 ± 3 |
3n | 25 ± 2 | 30 ± 5 | 11 ± 1 | Flumioxazin | 85 ± 6 | 92 ± 4 | 86 ± 6 |
Compd. | AR | DS |
---|---|---|
3a | 98 ± 2 | 61 ± 2 |
3d | 36 ± 3 | 0 |
Flumioxazin | 100 | 100 |
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Gao, W.; Li, X.; Ren, D.; Sun, S.; Huo, J.; Wang, Y.; Chen, L.; Zhang, J. Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors. Molecules 2019, 24, 4363. https://doi.org/10.3390/molecules24234363
Gao W, Li X, Ren D, Sun S, Huo J, Wang Y, Chen L, Zhang J. Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors. Molecules. 2019; 24(23):4363. https://doi.org/10.3390/molecules24234363
Chicago/Turabian StyleGao, Wei, Xiaotian Li, Da Ren, Susu Sun, Jingqian Huo, Yanen Wang, Lai Chen, and Jinlin Zhang. 2019. "Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors" Molecules 24, no. 23: 4363. https://doi.org/10.3390/molecules24234363