12N-Substituted Matrinol Derivatives Inhibited the Expression of Fibrogenic Genes via Repressing Integrin/FAK/PI3K/Akt Pathway in Hepatic Stellate Cells
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Target Compounds Inhibited the Expresion of COL1A1 Promotor in Human Hepatic Stellate LX-2 Cells
2.3. 8a Held a Good Safe Profile in LX-2 Cells
2.4. 8a Inhibited the Expressions of COL1A1 on mRNA and Protein Levels in Dose- and Time-dependent Manners
2.5. 8a Inhibited the Expressions of α-SMA on mRNA and Protein Levels in Time- and Dose-dependent Manner
2.6. 8a Inhibited the Expressions of Fibronectin on Protein Level in a Dose-Dependent Manner
2.7. 8a Inhibited the Expressions of TGFβ on mRNA and Protein Levels in Time and Dose-Dependent Manner
2.8. 8a Supressed the Intergrin-Focal Adhesion Pathway
3. Experimental Section
3.1. Apparatus, Materials, and Analysis Reagents
3.2. Chemistry
3.2.1. Synthesis of 12N-Benzoyl Matrinic Methyl Butyrate Hydrochloride (3b)
3.2.2. Synthesis of 12N-Benzenesulfonyl Matrinol Hydrochloride (4c)
3.2.3. General Procedure for the Synthesis of Compounds 7a–i
3.2.4. General Procedure for the Synthesis of Compounds 8a–i
3.3. Biology Assay
3.3.1. Cell Culture and Screening of Compounds
3.3.2. Sulforhodamine B (SRB) Assay
3.3.3. RT-qPCR Assay
3.3.4. Western Blot
3.3.5. Total mRNA Extraction
3.3.6. Genome Sequencing and Annotation
3.3.7. Gene Network/Pathway Analysis
3.3.8. Statistics
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 3a–c, 4a–c, 7a–i and 8a–i are available from the authors. |
Code | X | R1 | R2 | Inhibition Rate a |
---|---|---|---|---|
1 | - | - | - | 18.5% ± 1.1% |
3a | CH2 | H | COOCH3 | 24.7% ± 10.0% |
3b | CO | H | COOCH3 | 13.9% ± 8.3% |
3c | SO2 | H | COOCH3 | 30.6% ± 18.1% |
4a | CH2 | H | CH2OH | 31.5% ± 7.5% |
4b | CO | H | CH2OH | 21.6% ± 5.2% |
4c | SO2 | H | CH2OH | 13.9% ± 2.0% |
7a | NHCOCH2 | H | COOCH3 | 39.5% ± 7.1% |
7b | CH2NHCOCH2 | H | COOCH3 | 22.7% ± 8.5% |
7c | NHCOCH2 | p-F | COOCH3 | 45.2% ± 3.6% |
7d | NHCOCH2 | p-Cl | COOCH3 | 45.9% ± 2.2% |
7e | NHCOCH2 | p-Br | COOCH3 | 51.9% ± 3.1% |
7f | NHCOCH2 | p-CH3 | COOCH3 | 47.0% ± 9.8% |
7g | NHCOCH2 | p-CF3 | COOCH3 | 43.4% ± 11.2% |
7h | NHCOCH2 | p-NO2 | COOCH3 | 29.8% ± 9.2% |
7i | NHCOCH2 | 2,6-di-CH3 | COOCH3 | 24.0% ± 6.9% |
8a | NHCOCH2 | H | CH2OH | 51.0% ± 2.8% |
8b | CH2NHCOCH2 | H | CH2OH | 40.4% ± 5.2% |
8c | NHCOCH2 | p-F | CH2OH | 43.6% ± 1.8% |
8d | NHCOCH2 | p-Cl | CH2OH | 42.0% ± 19.2% |
8e | NHCOCH2 | p-Br | CH2OH | 50.6% ± 17.1% |
8f | NHCOCH2 | p-CH3 | CH2OH | 25.6% ± 5.6% |
8g | NHCOCH2 | p-CF3 | CH2OH | 32.3% ± 32.3% |
8h | NHCOCH2 | p-NO2 | C H2OH | 22.5% ± 13.0% |
8i | NHCOCH2 | 2,6-di-CH3 | CH2OH | 6.0% ± 14.5% |
EGCG b | - | - | - | 27.5% ± 7.9% |
DMSO | - | - | - | 2.9% ± 0 |
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Share and Cite
Bao, Y.; Pang, Y.; Tang, S.; Niu, T.; Guo, Z.; He, H.; Li, Y.; Song, D. 12N-Substituted Matrinol Derivatives Inhibited the Expression of Fibrogenic Genes via Repressing Integrin/FAK/PI3K/Akt Pathway in Hepatic Stellate Cells. Molecules 2019, 24, 3748. https://doi.org/10.3390/molecules24203748
Bao Y, Pang Y, Tang S, Niu T, Guo Z, He H, Li Y, Song D. 12N-Substituted Matrinol Derivatives Inhibited the Expression of Fibrogenic Genes via Repressing Integrin/FAK/PI3K/Akt Pathway in Hepatic Stellate Cells. Molecules. 2019; 24(20):3748. https://doi.org/10.3390/molecules24203748
Chicago/Turabian StyleBao, Yunyang, Yudong Pang, Sheng Tang, Tianyun Niu, Zhihao Guo, Hongwei He, Yinghong Li, and Danqing Song. 2019. "12N-Substituted Matrinol Derivatives Inhibited the Expression of Fibrogenic Genes via Repressing Integrin/FAK/PI3K/Akt Pathway in Hepatic Stellate Cells" Molecules 24, no. 20: 3748. https://doi.org/10.3390/molecules24203748