NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins
Abstract
:1. Introduction
2. Introduction
2.1. Synthesis of Compounds 2–9 and 10a–10i
2.2. Antiproliferative Activities in Vitro and SAR
2.3. NO-Releasing Ability
2.4. Effect of Cell Cycle
2.5. Induction of Apoptosis
2.6. Effect of Mitochondrial Depolarization
2.7. Effect of Apoptosis-Related Proteins
3. Materials and Methods
3.1. Chemistry
3.1.1. General
3.1.2. General Procedure to Synthesize 10
3.2. Biology
3.2.1. MTT Assay
3.2.2. Griess Assay
3.2.3. Cell Cycle Study
3.2.4. Analysis of Cellular Apoptosis
3.2.5. Mitochondrial Membrane Potential Assay
3.2.6. Western Blot Analysis
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
SAR | Structure Activity Relationship |
1H-NMR | Proton Nuclear Magnetic Resonance |
TMS | Tetramethylsilane |
MS | Mass Spectrometry |
ESI | Electrospray Ionization |
DCM | Dichloromethane |
MTT | 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
FBS | Fetal Bovine Serum |
NT | Not Test |
FITC | Fluorescein Isothiocyanate |
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- Sample Availability: Samples of the compounds 10a–i are available from the authors.
Compound | Bel-7402 | L-02 | K562 | MGC-803 | CaEs-17 |
---|---|---|---|---|---|
1 | 7.48 ± 0.32 | 18.3 ± 0.8 | 4.76 ± 0.32 | 5.69 ± 0.39 | 11.0 ± 1.0 |
9 | 16.0 ± 1.1 | 26.4 ± 1.3 | 2.64 ± 0.19 | 5.84 ± 0.57 | 23.7 ± 1.8 |
7a | 22.0 ± 0.8 | 37.8 ± 1.3 | 22.6 ± 2.0 | 25.4 ± 1.5 | 24.3 ± 0.9 |
7b | 22.3 ± 1.6 | 39.6 ± 1.4 | 24.2 ± 2.5 | 22.2 ± 2.5 | 25.7 ± 1.4 |
7c | 19.6 ± 1.0 | 41.3 ± 2.9 | 22.6 ± 1.7 | 24.6 ± 1.4 | 23.8 ± 1.0 |
7d | 17.8 ± 1.4 | 37.4 ± 0.8 | 17.5 ± 1.4 | 18.5 ± 0.8 | 19.8 ± 1.3 |
7e | 18.6 ± 0.8 | 36.3 ± 2.1 | 18.5 ± 1.6 | 20.0 ± 1.1 | 18.7 ± 1.0 |
7f | 16.7 ± 0.8 | 35.8 ± 1.3 | 17.5 ± 1.0 | 19.3 ± 0.6 | 19.2 ± 0.7 |
7g | 22.7 ± 1.0 | 39.4 ± 2.6 | 24.0 ± 1.4 | 20.6 ± 1.7 | 25.7 ± 0.7 |
7h | 21.3 ± 0.7 | 35.4 ± 1.4 | 24.5 ± 1.4 | 23.5 ± 1.0 | 22.9 ± 1.4 |
7i | 22.4 ± 1.6 | 37.9 ± 2.8 | 23.0 ± 1.2 | 21.6 ± 1.5 | 24.8 ± 1.5 |
10a | 1.91 ± 0.09 | 24.4 ± 0.8 | 2.86 ± 0.05 | 2.84 ± 1.12 | 5.68 ± 0.53 |
10b | 1.75 ± 0.12 | 22.1 ± 1.3 | 2.90 ± 0.17 | 2.67 ± 0.24 | 5.56 ± 0.06 |
10c | 1.01 ± 0.04 | 31.2 ± 1.2 | 1.97 ± 0.18 | 1.60 ± 0.15 | 4.02 ± 0.14 |
10d | 1.17 ± 0.02 | 27.4 ± 1.0 | 2.04 ± 0.10 | 2.03 ± 0.15 | 4.84 ± 0.47 |
10e | 1.12 ± 0.09 | 29.3 ± 0.9 | 2.02 ± 0.17 | 1.91 ± 0.09 | 4.04 ± 0.23 |
10f | 0.81 ± 0.06 | 29.9 ± 1.4 | 1.73 ± 0.04 | 1.18 ± 0.10 | 3.77 ± 0.30 |
10g | 1.85 ± 0.11 | 33.9 ± 1.5 | 2.82 ± 0.22 | 2.80 ± 0.09 | 5.52 ± 0.08 |
10h | 1.65 ± 0.12 | 29.8 ± 0.9 | 2.78 ± 0.20 | 2.65 ± 0.16 | 5.48 ± 0.21 |
10i | 1.09 ± 0.09 | 27.7 ± 1.3 | 2.06 ± 0.16 | 1.64 ± 0.12 | 4.13 ± 0.29 |
Taxol | 1.89 ± 0.09 | 3.73 ± 0.17 | 0.41 ± 0.02 | 4.65 ± 0.29 | 0.43 ± 0.03 |
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Li, D.; Hu, X.; Han, T.; Liao, J.; Xiao, W.; Xu, S.; Li, Z.; Wang, Z.; Hua, H.; Xu, J. NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins. Molecules 2016, 21, 1193. https://doi.org/10.3390/molecules21091193
Li D, Hu X, Han T, Liao J, Xiao W, Xu S, Li Z, Wang Z, Hua H, Xu J. NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins. Molecules. 2016; 21(9):1193. https://doi.org/10.3390/molecules21091193
Chicago/Turabian StyleLi, Dahong, Xu Hu, Tong Han, Jie Liao, Wei Xiao, Shengtao Xu, Zhanlin Li, Zhenzhong Wang, Huiming Hua, and Jinyi Xu. 2016. "NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins" Molecules 21, no. 9: 1193. https://doi.org/10.3390/molecules21091193