Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression
Abstract
:1. Introduction
2. Results
2.1. Design and Synthesis of Novel Curcumin Derivatives
2.2. Growth Inhibition of Human Tumor Cells and ROS Induction by Novel Curcumin Derivatives
2.3. Anti-Tumorigenic Activity of Novel Curcumin Derivatives
2.4. Clustering Analysis of Properties of Novel Curcumin Derivatives
2.5. Binding Properties of Novel Curcumin Derivatives to ROS Metabolic Enzymes and Clustering Analysis
2.6. Mode of Inhibitory Action of Novel Curcumin Derivatives on ROS Metabolic Enzymes
3. Discussion
4. Materials and Methods
4.1. Synthesis
4.1.1. C7-Curcuminoids, hs-031 and hs-037
4.1.2. 1-Aryl-1,3-diketones
4.1.3. C5-Curcuminoids
4.2. Proliferation Assays
4.3. Protein Analyses
4.4. CBR and GST Enzyme Assays
4.5. Tumorigenicity Test
4.6. Statistical Analysis
4.7. Prediction of Binding Sites of ROS Metabolic Enzymes for Curcumin and Curcumin Derivatives via a Docking Study
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Compound | CLogP (1) | Growth Suppression (2) | Cell Death (3) | 1/GI50 (4) | Washout Growth Suppression (5) | Tumor Suppression (6) |
---|---|---|---|---|---|---|
Curcumin | 2.94 | 4.83 | 10.80 | 0.08 | 20.00 | 100.00 |
hs-031 | 4.59 | 7.83 | 11.80 | 0.10 | 20.33 | 40.32 |
hs-037 | 1.91 | 8.33 | 15.00 | 0.31 | 28.00 | 95.16 |
hs-047 | 4.03 | −2.20 | 2.17 | 0.07 | −99.00 | −179.29 |
hs-054 | 1.81 | 3.17 | 8.00 | 0.08 | 15.20 | 10.16 |
hs-055 | 3.20 | 7.00 | 8.33 | 0.05 | 29.00 | 69.35 |
hs-056 | 3.35 | −23.80 | 1.33 | 0.03 | −98.00 | 85.48 |
hs-057 | 3.32 | 2.00 | 4.33 | 0.11 | −21.20 | 96.77 |
hs-062 | 1.88 | 5.33 | 1.33 | 0.06 | −24.50 | −101.61 |
hs-064 | 2.98 | 4.50 | 2.33 | 0.08 | 23.83 | 82.26 |
hs-073 | 2.47 | −20.70 | 0.50 | 0.03 | −101.00 | 17.74 |
hs-089 | 3.68 | 2.50 | 2.83 | 0.10 | 2.20 | 38.71 |
hs-140 | 2.65 | 8.50 | 4.83 | 0.06 | 12.00 | −206.45 |
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Nakamae, I.; Morimoto, T.; Shima, H.; Shionyu, M.; Fujiki, H.; Yoneda-Kato, N.; Yokoyama, T.; Kanaya, S.; Kakiuchi, K.; Shirai, T.; et al. Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression. Molecules 2019, 24, 4067. https://doi.org/10.3390/molecules24224067
Nakamae I, Morimoto T, Shima H, Shionyu M, Fujiki H, Yoneda-Kato N, Yokoyama T, Kanaya S, Kakiuchi K, Shirai T, et al. Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression. Molecules. 2019; 24(22):4067. https://doi.org/10.3390/molecules24224067
Chicago/Turabian StyleNakamae, Ikuko, Tsumoru Morimoto, Hiroki Shima, Masafumi Shionyu, Hisayo Fujiki, Noriko Yoneda-Kato, Takashi Yokoyama, Shigehiko Kanaya, Kiyomi Kakiuchi, Tsuyoshi Shirai, and et al. 2019. "Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression" Molecules 24, no. 22: 4067. https://doi.org/10.3390/molecules24224067