Natural amino acid conjugates of lithocholic acid as α-2,6-sialyltransferase inhibitors with antimigratory and antiangiogenic activity

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陳瑋昇(Wei-Sheng Chen) 查詢紙本館藏

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化學學系

論文名稱

(Natural amino acid conjugates of lithocholic acid as α-2,6-sialyltransferase inhibitors with antimigratory and antiangiogenic activity)

★ Synthesis and biological evaluation of pyrazole derivatives as antitumor agents

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摘要(中)

在這項工作中，石膽酸的氨基酸錯合物被設計、合成並評估了它們的細胞毒性、α-2,6-唾液酸轉移酶抑制、抗遷移和抗血管生成作用。在該系列中，具有色氨酸部分的 S1047 顯示可抑制 ST6GalI 活性（IC50 26.5 ± 1.2 μM）、抑制腫瘤生長、延遲癌細胞遷移並減少動物模型（生物體外）中的血管生成以及腫瘤生長。正在進行進一步研究以尋求石膽酸的氨基酸錯合物的臨床應用。

摘要(英)

In this work, the amino acid conjugates of lithocholic acid were designed, synthesized and evaluated their cytotoxicity, α-2,6-sialyltransferase inhibition, antimigratory and antiangiogenic effects. Among the series, S1047, possessing the tryptophan moiety, were shown to inhibit ST6GalI activity (IC50 26.5 ± 1.2 μM), suppress tumor growth, delay cancer cell migration, and reduce angiogenesis and tumor growth in animal model (ex vivo). Further study to pursue clinical application of amino acid conjugates of lithocholic acid is in progress.

關鍵字(中)

★ 唾液酸
★ 唾液酸轉移酶
★ 癌症轉移
★ 石膽酸

關鍵字(英)

★ sialic acid
★ sialyltransferase
★ metastasis
★ lithocholic acid

論文目次

摘要 I
Abstract II
Table of Contents III
List of Tables VI
List of Schemes VII
List of Abbreviation VIII
I. Introduction 1
1.1 Metastatic Process 1
1.2 The Correlation between Metastasis and Glycoconjugates 1
1.3 The Biosynthetic Process of Sialylation 2
1.4 Sialyltransferase 3
1.5 Sialyltransferase Inhibitors 4
1.6 Previous Works 6
1.7 Research Motivation 7
II. Results and Discussion 8
2.1 Chemistry 8
2.2 Cytotoxicity for LCA Derivatives 9
2.3 The Inhibition of ST3Gal I and ST6Gal 10
2.4 Anti-migration Effects 11
2.5 Anti-angiogenic Properties of S1047 14
2.6 Antiangiogenic Properties of S1047 on Mice Aortic Ring Assay 15
2.7 Animal Study 17
Ⅲ. Conclusions 20
Ⅳ. Materials and Methods 21
4.1 General Information 21
4.2 Experimental Method 22
4.2.1 Preparation of PEG linker 22
4.2.2 Synthesis of S1046 23
4.2.3 Synthesis of S1047 24
4.2.4 Synthesis of S1050 25
4.2.5 Synthesis of S1051 26
4.2.6 Synthesis of S1069 27
4.2.7 Synthesis of S1070 28
4.2.8 Synthesis of S1071 29
4.2.9 Synthesis of S1072 30
4.2.10 Synthesis of S1075 31
4.2.11 Synthesis of S1076 32
4.3 Cell Line Used and Cell Culture 34
4.4 MTT Cytotoxicity Analysis 34
V. References 35
VI. Spectra Appendix 38

參考文獻

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指導教授

李文山侯敦仁(Wen-Shan Li Duen-Ren Hou)

審核日期

2021-7-29

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