石膽酸二聚體對於唾液酸轉移酶及癌細胞轉移之影響

Abstract

本篇論文合成了具有不同的鏈及取代基的石膽酸二聚體類似物AK10165、AK10169、AK10172、AK10173、AK10181、AK10183、AK10184、AK10192、AK10194、AK10195、AK10196和AK10199，並且評估其細胞毒性、抑制唾液酸轉移酶能力，以及癌細胞轉移能力。綜上所述，石膽酸二聚體類似物幾乎沒有細胞毒性並顯示出對MDA-MB-231乳癌細胞的輕度抗轉移能力，其IC50為40 μM至80 μM。在這些石膽酸二聚體中，AK10165對ST6Gal I表現出最佳的抑制活性其IC50為18 μM。一系列的石膽酸二聚體也證明了輕微的唾液酸轉移酶抑制選擇性。更多的石膽酸二聚體臨床應用之近一步研究正在進行中。

In this work, the LCA dimer analogues AK10165, AK10169, AK10172, AK10173, AK10181, AK10183, AK10184, AK10192, AK10194, AK10195, AK10196 and AK10199 with different conjugate linkers and substituents were synthesized and evaluated their cytotox-icity, sialyltransferase isozyme inhibition, and anti-migration properties. To sum up, there is little cytotoxicity found in lithocholic acid dimer analogues, and mild anti-migratory capability were showed against MDA-MB-231 tumor cells, with IC50 ranging from 40 μM to 80 μM. Among these LCA dimers, AK10165 displayed the best inhibitory activity toward ST6Gal I with as IC50 value of 18 μM. A slight sialyltransferase isozyme selectivity is also demonstrated in their series of LCA dimers. Further study to pursue clinical application of LCA dimers is in progress.