Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Studies
2.2.1. Cytotoxicity Assay
2.2.2. Effects of Compound Treatment on Inflammatory Cytokine Secretion
2.2.3. Preliminary Structure Activity Relationship (SAR)
2.2.4. Dose Response Effects of Compound A2, A6, B7 on Inflammatory Cytokine Secretion
2.2.5. Inhibitory Effects of Compounds A2, A6, B7 on NO Production
2.2.6. Effects of Compounds A2, A6, B7 on iNOS and COX-2 Expression Levels
2.2.7. Effects of Compounds A2, A6, B7 on Cellular NF-κB p65 Translocation
2.2.8. Effects of Compounds A2, A6, B7 on MAPKs Phosphorylation in LPS-Stimulated RAW264.7 Cells
2.2.9. Effects of Compounds A2, A6, B7 Treatment on NF-κB Activation in LPS-Stimulated RAW264.7 Cells
2.2.10. Anti-Inflammatory Activity of A2, A6, and B7 in Carrageenan-Induced Rat Paw Edema
3. Materials and Methods
3.1. General
3.1.1. General Procedure for the Synthesis of 1
3.1.2. General Procedure for the Synthesis of A1–6
3.1.3. General Procedure for the Synthesis of 2 and 3
3.1.4. General Procedure for the Synthesis of B1–20
3.2. Cell Viability Assay
3.3. Determination of Cytokines
3.4. Measurement of NO Levels
3.5. RNA Isolation and Real-Time Reverse Transcription-Polymerase Chain Reaction (Real-Time RT-PCR)
- GAPDH (149 bp)
- (Sense primer) 5′ TATGTCGTGGAGTCTACTGGT 3′
- (Anti-sense primer) 5′ GAGTTGTCATATTTCTCGTGG 3′
- COX2 (74 bp)
- (Sense primer) 5′ TGAGCAACTATTCCAAACCAGC 3′
- (Anti-sense primer) 5′ GCACGTAGTCTTCGATCACTATC 3′
- INOS (127 bp)
- (Sense primer) 5′ GTTCTCAGCCCAACAATACAAGA 3′
- (Anti-sense primer) 5′ GTGGACGGGTCGATGTCAC 3′
3.6. Cellular NF-κB p65 Translocation Assay
3.7. Western Blot Analysis
3.8. Animal Study
3.9. Statistical Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Compound | R1 | Compound | R1 |
---|---|---|---|
A1 | A4 | ||
A2 | A5 | ||
A3 | A6 |
Compound | R2 | Compound | R2 |
---|---|---|---|
B1 | B11 | ||
B2 | B12 | ||
B3 | B13 | ||
B4 | B14 | ||
B5 | B15 | ||
B6 | B16 | ||
B7 | B17 | ||
B8 | B18 | ||
B9 | B19 | ||
B10 | B20 |
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Zhang, Y.; Luo, L.; Han, C.; Lv, H.; Chen, D.; Shen, G.; Wu, K.; Pan, S.; Ye, F. Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents. Molecules 2017, 22, 1960. https://doi.org/10.3390/molecules22111960
Zhang Y, Luo L, Han C, Lv H, Chen D, Shen G, Wu K, Pan S, Ye F. Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents. Molecules. 2017; 22(11):1960. https://doi.org/10.3390/molecules22111960
Chicago/Turabian StyleZhang, Yuan, Lu Luo, Chao Han, Handeng Lv, Di Chen, Guoliang Shen, Kaiqi Wu, Suwei Pan, and Faqing Ye. 2017. "Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents" Molecules 22, no. 11: 1960. https://doi.org/10.3390/molecules22111960
APA StyleZhang, Y., Luo, L., Han, C., Lv, H., Chen, D., Shen, G., Wu, K., Pan, S., & Ye, F. (2017). Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents. Molecules, 22(11), 1960. https://doi.org/10.3390/molecules22111960