Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biology
2.2.1. In Vitro Cytotoxic Effects
Comp. | IC50 (μM) a | ||||||
---|---|---|---|---|---|---|---|
7701QGY | SMMC7721 | HepG2 | CEM | CEM/VCR | K III | Lewis | |
4a | 3.28 ± 0.27 | 0.37 ± 0.07 | 4.74 ± 0.48 | 3.64 ± 0.35 | 9.65 ± 2.37 | 25.47 ± 2.95 | 2.26 ± 0.49 |
4b | 1.79 ± 0.26 | 0.04 ± 0.02 | 3.16 ± 0.39 | 0.37 ± 0.03 | 5.19 ± 0.64 | 13.58 ± 2.84 | 0.86 ± 0.10 |
4c | 10.09 ± 1.98 | 0.68 ± 0.05 | 5.54 ± 0.24 | 1.97 ± 0.09 | 17.54 ± 1.98 | 30.58 ± 1.69 | 2.86 ± 0.54 |
4d | 1.08 ± 0.25 | 0.02 ± 0.01 | 2.28 ± 0.37 | 0.16 ± 0.11 | 4.80 ± 0.81 | 10.41 ± 2.58 | 0.34 ± 0.09 |
berberine | 22.18 ± 1.12 | 2.09 ± 0.25 | 117.63 ± 3.13 | 45.04 ± 1.42 | 120.37 ± 3.84 | 84.29 ± 3.42 | 20.29 ± 4.42 |
palmatine | ND | 23.19 ± 1.21 | ND | 5.68 ± 0.27 | 230.76 ± 5.21 | 74.13 ± 4.50 | 30.18 ± 2.76 |
2.2.2. In Vivo Anticancer Activity
Comp. | Dose mg/kg | Injection | Number of mice | Weight of mice (g) | Weight of tumor X±SD (g) | Tumor inhibitory rate (%) | ||
---|---|---|---|---|---|---|---|---|
Start | End | Start | End | |||||
Control | - | iv | 10 | 10 | 19.48 ± 1.45 | 22.19 ± 2.20 | 2.20 ± 0.93 | - |
CP | 30 | iv | 10 | 10 | 20.23 ± 1.25 | 20.81 ± 2.31 | 0.43 ± 0.28 ** | 80.61 |
berberine | 30 | ip | 10 | 9 | 20.20 ± 1.26 | 17.66 ± 3.24 | 1.26 ± 0.54 ** | 42.99 |
4a | 1 | ip | 10 | 9 | 19.98 ± 1.33 | 17.86 ± 2.25 | 1.32 ± 0.63 ** | 40.00 |
2.5 | ip | 10 | 6 | 19.62 ± 1.52 | 18.04 ± 2.54 * | 1.01 ± 0.48 ** | 54.09 | |
4b | 1 | ip | 10 | 8 | 20.20 ± 2.22 | 19.17 ± 1.12 | 1.02 ± 0.25 ** | 53.52 |
2.5 | ip | 10 | 5 | 19.89 ± 1.54 | 17.11 ± 1.06 | 0.88 ± 0.28 ** | 59.86 | |
palmatine | 30 | ip | 10 | 10 | 20.56 ± 2.03 | 20.95 ± 2.18 | 1.45 ± 0.31 ** | 34.09 |
4c | 5 | ip | 10 | 10 | 20.33 ± 1.28 | 20.45 ± 1.45 | 1.43 ± 0.44 ** | 34.88 |
10 | ip | 10 | 9 | 19.16 ± 1.21 | 18.88 ± 2.60 * | 1.16 ± 0.44 ** | 47.40 | |
4d | 5 | ip | 10 | 9 | 20.72 ± 1.45 | 19.15 ± 2.75 | 1.28 ± 0.38 ** | 42.05 |
10 | ip | 10 | 5 | 20.04 ± 1.57 | 18.63 ± 3.20 | 1.08 ± 0.42 ** | 50.96 |
3. Experimental
3.1. General
3.2. Chemistry: General Procedure for the Synthesis of Compounds 4a–d
3.2. Pharmacology
3.2.1. MTT Assay
3.2.2. Anticancer Activity in Vivo
3.2.3. Statistical Analysis
4. Conclusions
Acknowledgments
References
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Zhang, L.; Li, J.; Ma, F.; Yao, S.; Li, N.; Wang, J.; Wang, Y.; Wang, X.; Yao, Q. Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents. Molecules 2012, 17, 11294-11302. https://doi.org/10.3390/molecules171011294
Zhang L, Li J, Ma F, Yao S, Li N, Wang J, Wang Y, Wang X, Yao Q. Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents. Molecules. 2012; 17(10):11294-11302. https://doi.org/10.3390/molecules171011294
Chicago/Turabian StyleZhang, Lei, Jingjing Li, Fei Ma, Shining Yao, Naisan Li, Jing Wang, Yongbin Wang, Xiuzhen Wang, and Qizheng Yao. 2012. "Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents" Molecules 17, no. 10: 11294-11302. https://doi.org/10.3390/molecules171011294