Design, Synthesis, and Biological Evaluation of Novel Benzo[b]thiophene 1,1-dioxide Derivatives as Potent STAT3 Inhibitors = Benzo[b]thiophene 1,1-dioxide 골격을 갖는 신규 STAT3 억제제 유도체 설계, 합성 및 생물학적 활성평가 연구

목차 (Table of Contents)

• Contents ⅰ
• List of Tables iii
• List of Figures iv
• List of Schemes v
• Abbreviations ⅴi
• Abstract viii
• Ⅰ. Introduction 1
• 1. Classification of STAT family 1
• 2. Organization of STAT3 structure 2
• 3. Canonical signaling pathway of STAT3 3
• 4. Strategies of STAT3 signaling pathway inhibition 4
• 5. Representative STAT3 small-molecule inhibitors 5
• Ⅱ. Results and Discussion 6
• 1. Rational design of benzo[b]thiophene 1,1-dioxide derivatives 6
• 2. Synthesis of benzo[b]thiophene 1,1-dioxide derivatives 7
• 3. Biological evaluation 8
• 3-1. Inhibitory activity against STAT3 transcription 8
• 3-2. Inhibitory activity against STAT3 phosphorylation 11
• 3-3. IC50 values against STAT3 transcription 13
• 3-4. Anti-proliferative activities of selected analogs on cancer cells 14
• 3-5. Inhibitory effect on the phosphorylation of STAT1 and STAT5 15
• 4. Structure-activity relationship based on molecular modeling study 17
• Ⅲ. Conclusion 19
• Ⅳ. Experimental Section 20
• 1. Synthesis 21
• 1-1. General procedures 21
• 1-2. Synthesis and characterization of compounds 22
• 2. Biological evaluation 38
• 2-1. Luciferase assay 38
• 2-2. Western blotting analysis 38
• 2-3. Cell counting kit-8 assay 38
• 2-4. Molecular docking simulations 39
• Ⅴ. References 40
• Ⅵ. Appendix 42
• Abstract in Korean 101