醣基化的Isomalyngamide A類似物作為抗轉移抑制劑的合成與初步生物活性之探討

Glycosylation of Isomalyngamide A Analogs with Different Linkers as Anti-migration Inhibitors: Synthesis and Preliminary Bioactivity Studies

黃建智(Chien-Chih Huang)

指導教授 ： 李文山

國立中正大學/理學院/化學暨生物化學系/碩士(2014年)

摘要

轉移是腫瘤細胞從原先位置轉移至其他器官，因此能發展出具有良好的抗轉移抑制劑，進而抑制腫瘤細胞從原先位置轉移至其他器官，是我們實驗室致力合成的目標。
本文所合成之isomalyngamide A 類似物，主要是以天然物isomalyngamide A結構做改變。我們以不同linkers及醣類化合物，合成出一系列的化合物，期望能找出其活性與結構間的關係。
將所合成之化合物作生物活性測試，以isomalyngamide 類似物4的活性結果為基準，利用MDA-MB-231 乳癌細胞進行細胞傷口癒合測試，發現AE-98、AE-105及AE-107具有抗轉移的潛力。

關鍵字

抗轉移

並列摘要

Metastasis is a combination of multiple biological events that results in migration of cancer cells from primary sites to secondary organs. Therefore, purposes and objectives of this study are making effort to develop effective anti-migration inhibitors and perhaps inhibit migration of cancer cells from primary sites to secondary organs in animal model in the near future.
In the thesis, we initially synthesized potential anti-migration inhibitors of the isomalyngamide A analogs. Then we used different linkers and sugars to design and prepare a series of compounds which are needed to evaluate their biological activities and strcture-activity relationship (SAR).
In wound healing assay, we found that compounds AE-98, AE-105, AE-107 possess potent anti-metastasis ability in comparison with the isomalyngamide analog 4, an anti-migration inhibitor.

並列關鍵字

isomalyngamide A

參考文獻

1.Han, B.; Reinscheid, U. M.; Gerwick, W. H.; Gross, H., The structure elucidation of isomalyngamide K from the marine cyanobacterium Lyngbya majuscula by experimental and DFT computational methods. J. Mol. Struct. 2011, 989 (1-3), 109-113.

2.Suntornchashwej, S.; Suwanborirux, K.; Koga, K.; Isobe, M., Malyngamide X: the first (7R)-lyngbic acid that connects to a new tripeptide backbone from the Thai sea hare Bursatella leachii. Chem. Asian J. 2007, 2 (1), 114-122.

3.Li, Y.; Feng, J. P.; Wang, W. H.; Chen, J.; Cao, X. P., Total synthesis and correct absolute configuration of malyngamide U. J. Org. Chem. 2007, 72 (7), 2344-2350.

4.Zhang Juntao, Qi Xianliang, Cao Xiaoping, Recent progress in the total synthesis of malyngamides. SCIENCEPAPER ONLINE 2011, 6 (12), 877-886.

5.Kan, Y.; Sakamoto, B.; Fujita, T.; Nagai, H., New malyngamides from the Hawaiian cyanobacterium Lyngbya majuscula. J. Nat. Prod. 2000, 63 (12), 1599-1602.