Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study
Abstract
:1. Introduction
2. Results
2.1. Synthesis of 3-((8Z,11E,13Z)-Pentadeca-8,11,13-Trien-1-yl) Benzene-1,2-Diol Derivatives
2.2. Anti-Tumor Bioactivity
2.3. QSAR (Quantitative Structure Activity Relationship)
2.4. Molecular Docking
2.4.1. Conjunction Conformation Score
2.4.2. Binding Pattern Analysis
2.5. Western Blot Results
2.6. Flow Cytometry Analysis
2.6.1. PI Single Staining Assay for Cell Cycle
2.6.2. Annexin-V FITC/PI Double Staining for Apoptosis
2.6.3. JC-1 Staining Assay Mitochondrial Membrane Potential
2.6.4. Calcium Ion Content Detection
2.7. Synergy
3. Experimental
3.1. Chemistry
3.2. Materials
3.3. Extraction and Synthesis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Cpd. | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 10 | 15 | 16 | 22 |
---|---|---|---|---|---|---|---|---|---|---|---|
HepG2 a | 28.6 | 63.2 | >200 | 2.8 | 39.5 | 25.0 | 6.0 | 28.9 | 29.4 | 23.9 | 65.8 |
LO2 b | 66.1 | 130.6 | >200 | 80.9 | >200 | 64.0 | 100.1 | 198.0 | >200 | >200 | 150.5 |
Compound | Pose | Grid Score | Grid_vdw | Grid_es | Int_energy |
---|---|---|---|---|---|
1 | 1 | −46.492264 | −40.641602 | −5.850661 | 4.597153 |
2 | 1 | −44.553402 | −40.142418 | −4.410985 | 9.792090 |
2 | −41.821983 | −36.967918 | −4.854066 | 7.414151 | |
3 | 1 | −47.741497 | −46.867558 | −0.873939 | 11.230281 |
4 | 1 | −70.507187 | −55.308952 | −15.198232 | 19.825512 |
2 | −68.278595 | −56.138966 | −12.139633 | 18.417746 | |
3 | −66.865288 | −53.072853 | −13.792435 | 11.982115 | |
5 | 1 | −50.337765 | −44.250916 | −6.086848 | 96.381271 |
6 | 1 | −45.127968 | −42.331528 | −2.796439 | 9.279520 |
7 | 1 | −72.713211 | −51.605087 | −21.108124 | 15.293597 |
10 | 1 | −44.027946 | −34.921326 | −9.106619 | 8.631289 |
2 | −42.797626 | −35.534809 | −7.262817 | 7.740744 | |
22 | 1 | −46.489151 | −41.222374 | −5.266776 | 9.209332 |
Compound | Pose | Grid Score | Grid_vdw | Grid_es | Int_energy |
---|---|---|---|---|---|
Ligand2 | 1 | −67.1829 | −44.7886 | −22.3944 | 13.1161 |
2 | −62.4968 | −48.8023 | −13.69444 | 16.3890 | |
3 | −62.2309 | −37.3300 | −24.90084 | 35.4859 |
Group | G1 (%) | S (%) | G2 (%) |
---|---|---|---|
CON | 48.06 | 35.8 | 16.14 |
1 μM | 55.92 | 32.46 | 11.62 |
3 μM | 58.06 | 32.36 | 9.57 |
12 μM | 63.84 | 18.76 | 17.4 |
Group | UL (%) | UR (%) | LL (%) | LR (%) | Apoptosis (%) |
---|---|---|---|---|---|
CON | 0.63 | 2.44 | 94.78 | 2.16 | 4.6 |
1 μM | 0.09 | 7.80 | 81.93 | 10.17 | 17.97 |
3 μM | 0.12 | 13.92 | 70.57 | 15.39 | 29.31 |
12 μM | 0.08 | 20.00 | 57.52 | 22.40 | 42.40 |
Group | Green Fluorescence (%) |
---|---|
CON | 5.80 |
1 μM | 13.16 |
3 μM | 27.03 |
12 μM | 49.32 |
Group | Mean |
---|---|
CON | 31.00 |
1 μM | 56.94 |
3 μM | 83.26 |
12 μM | 124.72 |
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Qi, Z.; Wang, C.; Jiang, J.; Wu, C. Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study. Int. J. Mol. Sci. 2018, 19, 3184. https://doi.org/10.3390/ijms19103184
Qi Z, Wang C, Jiang J, Wu C. Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study. International Journal of Molecular Sciences. 2018; 19(10):3184. https://doi.org/10.3390/ijms19103184
Chicago/Turabian StyleQi, Zhiwen, Chengzhang Wang, Jianxin Jiang, and Caie Wu. 2018. "Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study" International Journal of Molecular Sciences 19, no. 10: 3184. https://doi.org/10.3390/ijms19103184