Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Arabidopsis Growth Inhibitory Activity
2.3. Pre-Emergence Herbicidal Activity
2.4. Post-Emergence Herbicidal Activity
2.5. DXR Inhibitory Activity
2.6. DMAPP Rescue and Molecule Docking
2.7. Discussion on Structure–Activity Relationships
3. Materials and Methods
3.1. Instruments and Reagents
3.2. Synthesis
3.3. Biological Assays
3.3.1. Arabidopsis Growth Inhibition Assay
3.3.2. Pre-Emergence Herbicidal Inhibition Assay
3.3.3. Post-Emergence Herbicidal Inhibition Assay
3.3.4. DXR Enzyme Inhibition Assay
3.3.5. DMAPP Rescue
3.4. Molecular Docking
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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Entry | Base | PTC | Solvent | Temp (°C) | Yield (%) b |
1 | t-BuOK | -- | THF | r.t. | 60 |
2 | NaH | -- | THF | r.t. | 45 |
3 | NaOEt | -- | EtOH | r.t. | 40 |
4 | t-BuOK | -- | THF | 66 | 62 |
5 | DBU | -- | THF | r.t. | 50 |
6 | DBN | -- | THF | r.t. | 53 |
7 | Cs2CO3 | TBAI | CH3CN | 80 | 80 |
8 | Cs2CO3 | TEBAC | CH3CN | 80 | 85 |
9 | K2CO3 | TBAI | CH3CN | 80 | 83 |
10 | K2CO3 | TEBAC | CH3CN | 80 | 90 |
Comp | EC50 (mg/L) a | Comp | EC50 (mg/L) | Comp | EC50 (mg/L) |
---|---|---|---|---|---|
5a | >100 | 6f | >100 | 13b | 37.7 ± 2.8 |
5b | >100 | 12a | >100 | 13c | 48.4 ± 5.3 |
5c | >100 | 12b | >100 | 13d | 23.1 ± 1.9 |
5d | >100 | 12c | >100 | 13e | 7.8 ± 1.2 |
5e | >100 | 12d | >100 | 13f | 8.7 ± 1.3 |
5f | >100 | 12e | >100 | 13g | >100 |
6a | 28.6 ± 3.9 | 12f | >100 | 13h | >100 |
6b | >100 | 12g | >100 | 13i | 40.7 ± 2.9 |
6c | >100 | 12h | >100 | 19 | >100 |
6d | 45.7 ± 4.8 | 12i | 88.3 ± 4.3 | 20 | >100 |
6e | >100 | 13a | 21.6 ± 3.8 | FOS | 27.5 ± 3.1 |
Comp | EC50 (mg/L) | |||
---|---|---|---|---|
BN | EC | |||
Root | Stalk | Root | Stalk | |
6a | 17.3 | 10.5 | 24.0 | 18.9 |
6d | 67.5 | 38.2 | 40.1 | 25.7 |
12i | 36.6 | 21.7 | 53.1 | 47.7 |
13a | 26.9 | 8.5 | 27.1 | 10.2 |
13b | 38.8 | 20.2 | 29.9 | 35.3 |
13c | 27.7 | 46.9 | 43.9 | 45.8 |
13d | 25.2 | 11.0 | 27.2 | 13.5 |
13e | 10.7 | 2.3 | 7.4 | 4.1 |
13f | 17.9 | 5.8 | 9.7 | 3.6 |
13i | 40.5 | 33.5 | 32.1 | 34.6 |
19 | 79.3 | 39.2 | >100 | 88.0 |
20 | 34.6 | 8.2 | 40.0 | 25.2 |
FOS | 34.7 | 32.9 | 40.2 | 38.4 |
Comp | Visual Evaluation b | Loss of Weight (%) | ||
---|---|---|---|---|
AR | EC | AR | EC | |
6a | + | + | 35.6 | 30.8 |
13a | ++ | + | 52.3 | 35.8 |
13d | ++ | + | 45.7 | 34.9 |
13e | +++ | ++ | 70.3 | 53.5 |
13f | +++ | ++ | 61.8 | 48.1 |
20 | + | + | 23.6 | 22.9 |
FOS | + | + | 31.5 | 27.4 |
Comp | InR (%) a | Comp | InR (%) | Comp | InR (%) |
---|---|---|---|---|---|
5a | 11.9 | 6f | 11.7 | 13b | 27.4 |
5b | 12.9 | 12a | 13.7 | 13c | 28.4 |
5c | 6.1 | 12b | 21.9 | 13d | 14.0 |
5d | 17.7 | 12c | 32.3 | 13e | 54.9 |
5e | 23.0 | 12d | 12.4 | 13f | 24.4 |
5f | 32.4 | 12e | 22.8 | 13g | 7.3 |
6a | 15.8 | 12f | 6.1 | 13h | 10.3 |
6b | 19.5 | 12g | 11.6 | 13i | 30.3 |
6c | 7.5 | 12h | 2.3 | 19 | 22.5 |
6d | 17.3 | 12i | 27.1 | 20 | 29.5 |
6e | 12.1 | 13a | 60.2 | FOS | 98.7 |
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Wu, X.; Yang, Z.; Bu, M.; Duan, J.; Zhang, A. Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds. Molecules 2023, 28, 7509. https://doi.org/10.3390/molecules28227509
Wu X, Yang Z, Bu M, Duan J, Zhang A. Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds. Molecules. 2023; 28(22):7509. https://doi.org/10.3390/molecules28227509
Chicago/Turabian StyleWu, Xin, Zili Yang, Mengwei Bu, Jiang Duan, and Aidong Zhang. 2023. "Design, Synthesis and Bioactivity Evaluation of Heterocycle-Containing Mono- and Bisphosphonic Acid Compounds" Molecules 28, no. 22: 7509. https://doi.org/10.3390/molecules28227509