A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Biological Evaluation
2.2.1. Cytotoxic Effect of Oleanolic Acid Derivatives on HepG2.2.15 Cells
2.2.2. Activity against HBV Antigen Secretion in HepG2.2.15 Cells
2.2.3. Effects of OA-4 on HBV DNA Expression in HepG2.2.15 Cells
2.2.4. In Vivo Anti-HBV Activity of OA-4 in Ducks
3. Discussion
4. Materials and Methods
4.1. General Information
4.2. Chemistry
4.2.1. Preparation of OA-1
4.2.2. Preparation of OA-2 and OA-3
4.2.3. General Synthesis of the Compounds OA-4, OA-5 and OA-6
4.3. Cytotoxicity Evaluation
4.4. Assay of HBsAg and HBeAg Secretion
4.5. Quantification of HBV DNA in the Culture Medium
4.6. Experimental Inoculations of Ducklings
4.7. Dot Blot Analysis for DHBV DNA
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
DCM | dichloromethane |
NBS | N-bromosuccinimide |
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Compound | TC50 (µg/mL) | TC0 (µg/mL) |
---|---|---|
OA-1 | 38.15 | 8.64 |
OA-2 | >50 | >50 |
OA-3 | 37.82 | 7.21 |
OA-4 | 8.64 | 1.04 |
OA-5 | 33.25 | 6.41 |
OA-6 | 10.33 | 2.18 |
Compound | Concentration (μg/mL) | 3 Day | 6 Day | ||
---|---|---|---|---|---|
HBsAg (%) | HBeAg (%) | HBsAg (%) | HBeAg (%) | ||
OA-1 | 6.25 | 5.03 ± 1.42 | 10.57 ± 3.72 | 0.42 ± 1.56 | −10.01 ± 4.37 |
OA-2 | 6.25 | −11.96 ± 3.21 | −29.0 ± 0.46 | −6.67 ± 2.40 | −20.33 ± 7.53 |
OA-3 | 6.25 | 17.53 ± 3.09 | 1.15 ± 1.31 | 17.33 ± 4.74 | 3.56 ± 2.12 |
OA-4 | 1.56 | 36.48 ± 4.82 | 13.03 ± 3.17 | 20.21 ± 3.67 | 33.68 ± 4.03 |
OA-5 | 6.25 | 16.68 ± 4.64 | 6.78 ± 3.24 | 13.22 ± 2.83 | 8.54 ± 3.95 |
OA-6 | 1.56 | −15.50 ± 5.80 | −16.88 ± 5.96 | 3.76 ± 1.65 | −30.06 ± 7.32 |
3TC | 6.25 | 4.68 ± 2.73 | 6.31 ± 4.31 | 6.85 ± 2.58 | −16.12 ± 4.55 |
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Yan, W.; Zhang, C.; Li, B.; Xu, X.; Liang, M.; Gu, S.; Chu, F.; Xu, B.; Ren, J.; Wang, P.; Lei, H. A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation. Molecules 2016, 21, 402. https://doi.org/10.3390/molecules21040402
Yan W, Zhang C, Li B, Xu X, Liang M, Gu S, Chu F, Xu B, Ren J, Wang P, Lei H. A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation. Molecules. 2016; 21(4):402. https://doi.org/10.3390/molecules21040402
Chicago/Turabian StyleYan, Wenqiang, Chenze Zhang, Bi Li, Xin Xu, Miao Liang, Shun Gu, Fuhao Chu, Bing Xu, Jian Ren, Penglong Wang, and Haimin Lei. 2016. "A Series of Oleanolic Acid Derivatives as Anti-Hepatitis B Virus Agents: Design, Synthesis, and in Vitro and in Vivo Biological Evaluation" Molecules 21, no. 4: 402. https://doi.org/10.3390/molecules21040402