Discovery of Novel Tofacitinib–ADTOH Molecular Hybridization Derivatives for the Treatment of Ulcerative Colitis
Abstract
:1. Introduction
2. Experimental Section
2.1. Chemistry Section
2.1.1. General Synthetic Procedure A for Intermediates 3a–c
2.1.2. General Synthetic Procedure B for Intermediates 4a–c
2.1.3. Synthetic Procedure for Intermediate 7
2.1.4. General Synthetic Procedure C for Intermediates 8a–c
2.1.5. General Synthetic Procedure D for Intermediates 9a–c
2.1.6. Synthetic Procedure for Intermediate 12
2.1.7. General Synthetic Procedure E for Target Compounds ZX-4C~ZX-6C
2.2. Evaluation of Hydrogen Sulfide Release
2.3. Fluorescent Probe to Study H2S Release in Cultured Cells
2.4. Esterase-Responsive Drug Release as Monitored by HPLC
2.5. Cell Culture
2.6. Cell Viability Assay
2.7. Detection of ROS Levels
2.8. Detection of GPx, SOD Activities, and GSH/GSSG Ratio
2.9. Detection of IL-1β, IL-6, and TNF-α Production
2.10. In Vivo Studies
2.11. Histopathological Assessment
2.12. Statistical Analysis
3. Results and Discussion
3.1. Molecular Hybridization Strategy to Design Tofacitinib–ADTOH Hybrid Derivatives
3.2. Chemistry
3.3. H2S Release Efficiency of Compounds ZX-4C~ZX-6C
3.4. ZX-4C Exhibited Protective Effects Against DSS-Induced Injury in NCM460 Cells
3.5. ZX-4C Alleviated DSS-Induced Colitis in Mice
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Mou, Y.; Wen, S.; Wang, Y.; Zhao, Y.; Li, Y.-P.; Sha, H.-K.; Gui, L.-J.; Jiang, Z.-Y.; Xu, X.-M. Discovery of Novel Tofacitinib–ADTOH Molecular Hybridization Derivatives for the Treatment of Ulcerative Colitis. Antioxidants 2025, 14, 325. https://doi.org/10.3390/antiox14030325
Mou Y, Wen S, Wang Y, Zhao Y, Li Y-P, Sha H-K, Gui L-J, Jiang Z-Y, Xu X-M. Discovery of Novel Tofacitinib–ADTOH Molecular Hybridization Derivatives for the Treatment of Ulcerative Colitis. Antioxidants. 2025; 14(3):325. https://doi.org/10.3390/antiox14030325
Chicago/Turabian StyleMou, Yi, Shuai Wen, Yan Wang, Yao Zhao, Ying-Ping Li, Hong-Kai Sha, Li-Juan Gui, Zheng-Yu Jiang, and Xiang-Ming Xu. 2025. "Discovery of Novel Tofacitinib–ADTOH Molecular Hybridization Derivatives for the Treatment of Ulcerative Colitis" Antioxidants 14, no. 3: 325. https://doi.org/10.3390/antiox14030325
APA StyleMou, Y., Wen, S., Wang, Y., Zhao, Y., Li, Y.-P., Sha, H.-K., Gui, L.-J., Jiang, Z.-Y., & Xu, X.-M. (2025). Discovery of Novel Tofacitinib–ADTOH Molecular Hybridization Derivatives for the Treatment of Ulcerative Colitis. Antioxidants, 14(3), 325. https://doi.org/10.3390/antiox14030325