Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities
Abstract
:1. Introduction
2. Chemistry
3. Results and Discussion
3.1. HDAC1 Inhibitory Activity of Synthesized Compounds
3.2. Antiproliferative Activity
3.3. Colony Formation Assay
3.4. Western Blot Analysis
3.5. Anti-Migration Assay
3.6. Cell Cycle Arrest Analysis
3.7. Apoptosis Analysis
3.8. Molecular Docking Studies
4. Experimental Section
4.1. Materials and Methods
4.2. General Procedures for Synthesis of 13a–g and 14a–s
4.3. HDAC1 Inhibitory Assay
4.4. Cell Culture and Reagents
4.5. Colony Formation Assay
4.6. Western Blot Analysis
4.7. Anti-Migration Assay
4.8. Cell Cycle Arrest Analysis and Apoptosis Analysis
4.9. Molecular Docking Studies
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of compounds 13a–g and 14a–s are available from the authors. |
Compounds | R | IC50 (nM) |
---|---|---|
13a | 0.48 | |
13b | 0.31 | |
13c | 0.30 | |
13d | 0.33 | |
13e | 0.77 | |
13f | 0.60 | |
13g | 5.01 | |
14a | 0.96 | |
14b | 1.59 | |
14c | 1.97 | |
14d | 1.72 | |
14e | 0.75 | |
14f | 0.99 | |
14g | 0.88 | |
14h | 2.40 | |
14i | 4.25 | |
14j | 2.52 | |
14k | 3.02 | |
14l | 5.50 | |
14m | 0.50 | |
14n | 0.78 | |
14o | 3.22 | |
14p | 1.56 | |
14q | 2.95 | |
14r | 2.50 | |
14s | 5.19 | |
7 | 1.85 | |
1 | 12.36 |
Compounds | MDA-MB-231 | H157 | A549 | MCF-7 |
---|---|---|---|---|
13a | 0.73 ± 0.23 | 1.04 ± 0.08 | 5.62 ± 1.21 | 2.91 ± 0.43 |
13b | 1.97 ± 0.56 | 1.20 ± 0.17 | 4.09 ± 1.54 | 2.93 ± 0.49 |
13c | 0.36 ± 0.08 | 0.59 ± 0.03 | 2.79 ± 0.87 | 1.84 ± 0.17 |
13d | 1.70 ± 0.39 | 2.36 ± 0.50 | 4.11 ± 0.65 | 5.23 ± 1.63 |
14m | 1.95 ± 0.29 | 4.81 ± 0.8 | 7.58 ± 2.05 | 6.05 ± 1.33 |
1 | 1.33 ± 0.61 | 1.66 ± 0.14 | 5.34 ± 1.09 | 4.15 ± 0.74 |
Compounds | Beas-2B | L-02 |
---|---|---|
13a | >50 | >50 |
13b | >50 | >20 |
13c | >100 | >100 |
13d | >20 | >20 |
1 | >50 | >50 |
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Zhao, N.; Yang, F.; Han, L.; Qu, Y.; Ge, D.; Zhang, H. Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities. Molecules 2020, 25, 717. https://doi.org/10.3390/molecules25030717
Zhao N, Yang F, Han L, Qu Y, Ge D, Zhang H. Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities. Molecules. 2020; 25(3):717. https://doi.org/10.3390/molecules25030717
Chicago/Turabian StyleZhao, Na, Feifei Yang, Lina Han, Yuhua Qu, Di Ge, and Hua Zhang. 2020. "Development of Coumarin-Based Hydroxamates as Histone Deacetylase Inhibitors with Antitumor Activities" Molecules 25, no. 3: 717. https://doi.org/10.3390/molecules25030717